Vaccines

9 pages, 855 KiB

Open AccessArticle

CD19⁺ CD24^hi CD38^hi Regulatory B Cells and Memory B Cells in Periodontitis: Association with Pro-Inflammatory and Anti-Inflammatory Cytokines

by Helal F. Hetta, Ibrahim M. Mwafey, Gaber El-Saber Batiha, Suliman Y. Alomar, Nahed A. Mohamed, Maggie A. Ibrahim, Abeer Elkady, Ahmed Kh. Meshaal, Hani Alrefai, Dina M. Khodeer and Asmaa M. Zahran

Vaccines 2020, 8(2), 340; https://doi.org/10.3390/vaccines8020340 - 26 Jun 2020

Cited by 21 | Viewed by 3519

Abstract

Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Due to the current limitations of human Breg studies among periodontal diseases, in the present study, we tried to analyze the [...] Read more.

Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Due to the current limitations of human Breg studies among periodontal diseases, in the present study, we tried to analyze the change in circulating Bregs, pro-inflammatory, and anti-inflammatory cytokines in patients with periodontitis. Peripheral blood from 55 patients with stage 2 periodontitis and 20 healthy controls was analyzed using flow cytometry to evaluate the frequency of CD19⁺CD24⁺CD38⁺ Breg cells. ELISA was used to assess the serum levels of the pro-inflammatory cytokines, including interleukins (IL)-1β, IL-6, TNF-α, and anti-inflammatory cytokines including IL-10, IL-35, and TGF-β. Increased proportions of Breg cells were observed in patients with stage 2 periodontitis compared to controls. Serum levels of cytokines were significantly higher in patients with periodontitis compared to controls. A significant positive correlation was observed between the frequencies of Breg cells and IL35 levels, IL10 levels, and TGF-β. In conclusion, our results suggest that the increase in peripheral Breg cells and serum cytokine levels among periodontitis patients seems to be closely associated with disease progression, a possible link between periodontitis, and systemic inflammatory process. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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13 pages, 1614 KiB

Open AccessArticle

Cross-Sectional Study on the Sero- and Viral Dynamics of Porcine Circovirus Type 2 in the Field

by Chao-Nan Lin, Ni-Jyun Ke and Ming-Tang Chiou

Vaccines 2020, 8(2), 339; https://doi.org/10.3390/vaccines8020339 - 26 Jun 2020

Cited by 10 | Viewed by 2881

Abstract

Porcine circovirus-associated diseases (PCVADs) cause considerable economic losses in industrial pork production in the field. To minimize the economic losses due to PCVAD, porcine circovirus type 2 (PCV2) vaccines have been developed, and there is widespread vaccination worldwide today. However, limited information is [...] Read more.

Porcine circovirus-associated diseases (PCVADs) cause considerable economic losses in industrial pork production in the field. To minimize the economic losses due to PCVAD, porcine circovirus type 2 (PCV2) vaccines have been developed, and there is widespread vaccination worldwide today. However, limited information is available concerning the current status of PCV2 infection in the field on the Asian continent. The present study aimed to assess sero- and viral dynamics of PCV2 from 12 PCV2-contaminated pig herds with vaccination against PCV2 in Southern and Central Taiwan. In particular, the level of PCV2 load during the window period for seroconversion using real-time polymerase chain reaction and a commercial enzyme-linked immunosorbent assay (ELISA) kit. Our results revealed that pig herds showed slight or no seroconversion after three to four weeks post-PCV2 immunization. The presence of PCV2 was observed during the window period for seroconversion in all herds. In conclusion, natural exposure of PCV2 occurs in the growing to fattening period, and viremia can last until slaughter. Additionally, our findings indicate that using ELISA showed the level of antibodies and aided in the understanding and surveillance of the current PCV2 status in the field. Full article

(This article belongs to the Section Veterinary Vaccines)

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24 pages, 1926 KiB

Open AccessArticle

Establishing a Robust Manufacturing Platform for Recombinant Veterinary Vaccines: An Adenovirus-Vector Vaccine to Control Newcastle Disease Virus Infections of Poultry in Sub-Saharan Africa

by Omar Farnós, Esayas Gelaye, Khaled Trabelsi, Alice Bernier, Kumar Subramani, Héla Kallel, Martha Yami and Amine A. Kamen

Vaccines 2020, 8(2), 338; https://doi.org/10.3390/vaccines8020338 - 26 Jun 2020

Cited by 7 | Viewed by 5905

Abstract

Developing vaccine technology platforms to respond to pandemic threats or zoonotic diseases is a worldwide high priority. The risk of infectious diseases transmitted from wildlife and domestic animals to humans makes veterinary vaccination and animal health monitoring highly relevant for the deployment of [...] Read more.

Developing vaccine technology platforms to respond to pandemic threats or zoonotic diseases is a worldwide high priority. The risk of infectious diseases transmitted from wildlife and domestic animals to humans makes veterinary vaccination and animal health monitoring highly relevant for the deployment of public health global policies in the context of “one world, one health” principles. Sub-Saharan Africa is frequently impacted by outbreaks of poultry diseases such as avian influenza and Newcastle Disease (ND). Here, an adenovirus-vectored vaccine technology platform is proposed for rapid adaptation to ND or other avian viral threats in the region. Ethiopian isolates of the Newcastle Disease virus (NDV) were subjected to sequence and phylogenetic analyses, enabling the construction of antigenically matched vaccine candidates expressing the fusion (F) and hemagglutinin-neuraminidase (HN) proteins. A cost-effective vaccine production process was developed using HEK293 cells in suspension and serum-free medium. Productive infection in bioreactors (1–3 L) at 2 × 10⁶ cells/mL resulted in consistent infectious adenoviral vector titers of approximately 5–6 × 10⁸ TCID₅₀/mL (approximately 10¹¹VP/mL) in the harvest lysates. Groups of chickens were twice immunized with 1 × 10¹⁰ TCID₅₀ of the vectors, and full protection against a lethal NDV challenge was provided by the vector expressing the F antigen. These results consolidate the basis for a streamlined and scalable-vectored vaccine manufacturing process for deployment in low- and medium-income countries. Full article

(This article belongs to the Special Issue Genomic Medicine and Advances in Vaccine Technology and Development in the Developing and Developed World)

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21 pages, 3021 KiB

Open AccessArticle

Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

by Kristina Borochova, Katarzyna Niespodziana, Katarina Stenberg Hammar, Marianne van Hage, Gunilla Hedlin, Cilla Söderhäll, Margarete Focke-Tejkl and Rudolf Valenta

Vaccines 2020, 8(2), 337; https://doi.org/10.3390/vaccines8020337 - 25 Jun 2020

Cited by 5 | Viewed by 3226

Abstract

Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies [...] Read more.

Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection. We expressed the surface-exposed part of A2 strain-derived G (A2-G) in baculovirus-infected insect cells and synthesized overlapping peptides spanning complete A2-G. The investigation of the natural IgG response of adult subjects during a period of one year showed that IgG antibodies (i) recognize G significantly stronger than the fusion protein F0, (ii) target mainly non-conformational, sequential peptide epitopes from the exposed conserved region but also buried peptides, and (iii) exhibit a scattered but constant recognition profile during the observation period. The IgG subclass reactivity profile (IgG₁ > IgG₂ > IgG₄ = IgG₃) was indicative of a mixed Th1/Th2 response. Two strongly RSV-neutralizing sera including the 1st WHO standard contained high IgG anti-G levels. G-specific IgG increased strongly in children after wheezing attacks suggesting RSV as trigger factor. Our study shows that RSV G and G-derived peptides are useful for serological diagnosis of RSV-triggered exacerbations of respiratory diseases and underlines the importance of G for development of RSV-neutralizing vaccines. Full article

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14 pages, 1682 KiB

Open AccessArticle

How to Demonstrate Freedom from African Swine Fever in Wild Boar—Estonia as an Example

by Katja Schulz, Christoph Staubach, Sandra Blome, Imbi Nurmoja, Arvo Viltrop, Franz J. Conraths, Maarja Kristian and Carola Sauter-Louis

Vaccines 2020, 8(2), 336; https://doi.org/10.3390/vaccines8020336 - 25 Jun 2020

Cited by 23 | Viewed by 3662

Abstract

Estonia has been combatting African swine fever (ASF) for six years now. Since October 2017, the disease has only been detected in the wild boar population, but trade restrictions had to remain in place due to international regulations. Yet, the epidemiological course of [...] Read more.

Estonia has been combatting African swine fever (ASF) for six years now. Since October 2017, the disease has only been detected in the wild boar population, but trade restrictions had to remain in place due to international regulations. Yet, the epidemiological course of the disease has changed within the last few years. The prevalence of ASF virus (ASFV)-positive wild boar decreased steadily towards 0%. In February 2019, the last ASFV-positive wild boar was detected. Since then, positive wild boar samples have exclusively been positive for ASFV-specific antibodies, suggesting the possible absence of circulating ASFV in the Estonian wild boar population. However, as the role of seropositive animals is controversially discussed and the presence of antibody-carriers is regarded as an indication of virus circulation at EU and OIE level, Estonia remains under trade restrictions. To make the disease status of a country reliable for trading partners and to facilitate the process of declaration of disease freedom, we suggest to monitor the prevalence of seropositive wild boar in absence of ASFV-positive animals. The possibility to include ASF in the list of diseases, for which an official pathway for recognition of disease status is defined by the OIE should be evaluated. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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33 pages, 3655 KiB

Open AccessReview

SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries

by Hatem A. Elshabrawy

Vaccines 2020, 8(2), 335; https://doi.org/10.3390/vaccines8020335 - 23 Jun 2020

Cited by 34 | Viewed by 8445

Abstract

Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases [...] Read more.

Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs. Full article

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15 pages, 758 KiB

Open AccessArticle

Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

by Christel Protiere, Lisa Fressard, Marion Mora, Laurence Meyer, Marie Préau, Marie Suzan-Monti, Jean-Daniel Lelièvre, Olivier Lambotte, Bruno Spire and the APSEC Study Group

Vaccines 2020, 8(2), 334; https://doi.org/10.3390/vaccines8020334 - 23 Jun 2020

Cited by 5 | Viewed by 2824

Abstract

HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians’ motivations to propose HCRCT to patients. Between October 2016 and March [...] Read more.

HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians’ motivations to propose HCRCT to patients. Between October 2016 and March 2017, 164 French HIV physicians were asked about their level of agreement with four viewpoints regarding HCRCT. A reluctance score was derived from their answers and factors associated with reluctance identified. Results showed the highest reluctance to propose HCRCT was among physicians with a less research-orientated professional activity, those not informing themselves about cure trials through scientific literature, and those who participated in trials because their department head asked them. Physicians’ perceptions of the impact of HIV on their patients’ lives were also associated with their motivation to propose HCRCT: those who considered that living with HIV means living with a secret were more motivated, while those worrying about the negative impact on person living with HIV’s professional lives were more reluctant. Our study highlighted the need to design a HCRCT that minimizes constraints for participants and for continuous training programs to help physicians keep up-to-date with recent advances in HIV cure research. Full article

(This article belongs to the Special Issue Therapeutic Vaccination of HIV-infected Patients)

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19 pages, 8891 KiB

Open AccessArticle

Activation of OX40 and CD27 Costimulatory Signalling in Sheep through Recombinant Ovine Ligands

by José Manuel Rojas, Alí Alejo, Jose Miguel Avia, Daniel Rodríguez-Martín, Carolina Sánchez, Antonio Alcamí, Noemí Sevilla and Verónica Martín

Vaccines 2020, 8(2), 333; https://doi.org/10.3390/vaccines8020333 - 22 Jun 2020

Cited by 4 | Viewed by 3076

Abstract

Members of the tumour necrosis factor (TNF) superfamily OX40L and CD70 and their receptors are costimulating signalling axes critical for adequate T cell activation in humans and mice but characterisation of these molecules in other species including ruminants is lacking. Here we cloned [...] Read more.

Members of the tumour necrosis factor (TNF) superfamily OX40L and CD70 and their receptors are costimulating signalling axes critical for adequate T cell activation in humans and mice but characterisation of these molecules in other species including ruminants is lacking. Here we cloned and expressed the predicted ovine orthologues of the receptors OX40 and CD27, as well as soluble recombinant forms of their potential ovine ligands, OaOX40L and OaCD70. Using biochemical and immunofluorescence analyses, we show that both signalling axes are functional in sheep. We show that oligomeric recombinant ligand constructs are able to induce signalling through their receptors on transfected cells. Recombinant defective human adenoviruses were constructed to express the soluble forms of OaOX40L and OaCD70. Both proteins were detected in the supernatant of adenovirus-infected cells and shown to activate NF-κB signalling pathway through their cognate receptor. These adenovirus-secreted OaOX40L and OaCD70 forms could also activate ovine T cell proliferation and enhance IFN-γ production in CD4⁺ and CD8⁺ T cells. Altogether, this study provides the first characterisation of the ovine costimulatory OX40L-OX40 and CD70-CD27 signalling axes, and indicates that their activation in vivo may be useful to enhance vaccination-induced immune responses in sheep and other ruminants. Full article

(This article belongs to the Section Cellular/Molecular Immunology)

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16 pages, 1678 KiB

Open AccessArticle

Nitric Oxide Production and Fc Receptor-Mediated Phagocytosis as Functional Readouts of Macrophage Activity upon Stimulation with Inactivated Poultry Vaccines In Vitro

by Robin H.G.A. van den Biggelaar, Willem van Eden, Victor P.M.G. Rutten and Christine A. Jansen

Vaccines 2020, 8(2), 332; https://doi.org/10.3390/vaccines8020332 - 22 Jun 2020

Cited by 7 | Viewed by 4436

Abstract

Vaccine batches must pass routine quality control to confirm that their ability to induce protection against disease is consistent with batches of proven efficacy from development studies. For poultry vaccines, these tests are often performed in laboratory chickens by vaccination-challenge trials or serological [...] Read more.

Vaccine batches must pass routine quality control to confirm that their ability to induce protection against disease is consistent with batches of proven efficacy from development studies. For poultry vaccines, these tests are often performed in laboratory chickens by vaccination-challenge trials or serological assays. The aim of this study was to investigate innate immune responses against inactivated poultry vaccines and identify candidate immune parameters for in vitro quality tests as alternatives for animal-based quality tests. For this purpose, we set up assays to measure nitric oxide production and phagocytosis by the macrophage-like cell line HD11, upon stimulation with inactivated poultry vaccines for infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and egg drop syndrome virus (EDSV). In both assays, macrophages became activated after stimulation with various toll-like receptor agonists. Inactivated poultry vaccines stimulated HD11 cells to produce nitric oxide due to the presence of mineral oil adjuvant. Moreover, inactivated poultry vaccines were found to enhance Fc receptor-mediated phagocytosis due to the presence of allantoic fluid in the vaccine antigen preparations. We showed that inactivated poultry vaccines stimulated nitric oxide production and Fc receptor-mediated phagocytosis by chicken macrophages. Similar to antigen quantification methods, the cell-based assays described here can be used for future assessment of vaccine batch-to-batch consistency. The ability of the assays to determine the immunopotentiating properties of inactivated poultry vaccines provides an additional step in the replacement of current in vivo batch-release quality tests. Full article

(This article belongs to the Special Issue Poultry Vaccines)

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6 pages, 622 KiB

Open AccessCommunication

Risk Assessment and Virological Monitoring Following an Accidental Exposure to Concentrated Sabin Poliovirus Type 3 in France, November 2018

by Marion Jeannoël, Denise Antona, Clément Lazarus, Bruno Lina and Isabelle Schuffenecker

Vaccines 2020, 8(2), 331; https://doi.org/10.3390/vaccines8020331 - 22 Jun 2020

Cited by 2 | Viewed by 2436

Abstract

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of [...] Read more.

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of containment have already been documented. Here, we report the management of an incident that occurred on 30 November 2018 in a French vaccine manufacturing plant. Five adequately vaccinated operators were exposed to a Sabin poliovirus type 3 (PV3) spill. A microbiological risk assessment was conducted and the operators were monitored for PV shedding. On day 5 after exposure, Sabin PV3 was detected only in the stool sample of the most exposed worker. Shedding of Sabin PV3 (as detected by viral culture) was restricted to a very short period (less than 15 days). Monitoring of this incident was an opportunity to assess the relevance of our national response plan. We concluded that the measures undertaken and reported here were appropriate and proportional. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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19 pages, 2291 KiB

Open AccessArticle

Limited Cross-Protection against Infectious Bronchitis Provided by Recombinant Infectious Bronchitis Viruses Expressing Heterologous Spike Glycoproteins

by Sarah Keep, Samantha Sives, Phoebe Stevenson-Leggett, Paul Britton, Lonneke Vervelde and Erica Bickerton

Vaccines 2020, 8(2), 330; https://doi.org/10.3390/vaccines8020330 - 22 Jun 2020

Cited by 8 | Viewed by 4335

Abstract

Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult [...] Read more.

Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult to predict. In this study, the ability of two recombinant IBV vaccine candidates, BeauR-M41(S) and BeauR-4/91(S), to induce cross-protection against a third serotype, QX, was assessed. Both rIBVs are genetically based on the Beaudette genome with only the S gene derived from either M41 or 4/91, two unrelated serotypes. The use of these rIBVs allowed for the assessment of the potential of M41 and 4/91 S glycoproteins to induce cross-protective immunity against a heterologous QX challenge. The impact of the order of vaccination was also assessed. Homologous primary and secondary vaccination with BeauR-M41(S) or BeauR-4/91(S) resulted in a significant reduction of infectious QX load in the trachea at four days post-challenge, whereas heterologous primary and secondary vaccination with BeauR-M41(S) and BeauR-4/91(S) reduced viral RNA load in the conjunctiva-associated lymphoid tissue (CALT). Both homologous and heterologous vaccination regimes reduced clinical signs and birds recovered more rapidly as compared with an unvaccinated/challenge control group. Despite both rIBV BeauR-M41(S) and BeauR-4/91(S) displaying limited replication in vivo, serum titres in these vaccinated groups were higher as compared with the unvaccinated/challenge control group. This suggests that vaccination with rIBV primed the birds for a boosted humoral response to heterologous QX challenge. Collectively, vaccination with the rIBV elicited limited protection against challenge, with failure to protect against tracheal ciliostasis, clinical manifestations, and viral replication. The use of a less attenuated recombinant vector that replicates throughout the respiratory tract could be required to elicit a stronger and prolonged protective immune response. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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17 pages, 986 KiB

Open AccessReview

Modulation of Anti-Tumour Immune Responses by Probiotic Bacteria

by Georgios Aindelis and Katerina Chlichlia

Vaccines 2020, 8(2), 329; https://doi.org/10.3390/vaccines8020329 - 21 Jun 2020

Cited by 17 | Viewed by 5421

Abstract

There is a growing amount of evidence to support the beneficial role of a balanced intestinal microbiota, or distinct members thereof, in the manifestation and progression of malignant tumours, not only in the gastrointestinal tract but also in distant tissues as well. Intriguingly, [...] Read more.

There is a growing amount of evidence to support the beneficial role of a balanced intestinal microbiota, or distinct members thereof, in the manifestation and progression of malignant tumours, not only in the gastrointestinal tract but also in distant tissues as well. Intriguingly, bacterial species have been demonstrated to be indispensable modulatory agents of widely-used immunotherapeutic or chemotherapeutic regiments. However, the exact contribution of commensal bacteria to immunity, as well as to neoplasia formation and response to treatment, has not been fully elucidated, and most of the current knowledge acquired from animal models has yet to be translated to human subjects. Here, recent advances in understanding the interaction of gut microbes with the immune system and the modulation of protective immune responses to cancer, either naturally or in the context of widely-used treatments, are reviewed, along with the implications of these observations for future therapeutic approaches. In this regard, bacterial species capable of facilitating optimal immune responses against cancer have been surveyed. According to the findings summarized here, we suggest that strategies incorporating probiotic bacteria and/or modulation of the intestinal microbiota can be used as immune adjuvants, aiming to optimize the efficacy of cancer immunotherapies and conventional anti-tumour treatments. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

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9 pages, 1295 KiB

Open AccessArticle

Seroprevalence of Neutralizing Antibodies against Japanese Encephalitis Virus among Adolescents and Adults in Korea: A Prospective Multicenter Study

by Byung Ok Kwak, Young Se Kwon, Young Jin Hong, Chung Hyun Nahm, Woori Jang, Young Uh, Yong Gon Cho, Jimyung Kim, Myungshin Kim and Dong Hyun Kim

Vaccines 2020, 8(2), 328; https://doi.org/10.3390/vaccines8020328 - 19 Jun 2020

Cited by 7 | Viewed by 3013

Abstract

The immunization schedule for the Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12–24 months of age, followed by booster doses 12 months after the second dose and at the ages of 6 and 12 years. Although the number [...] Read more.

The immunization schedule for the Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12–24 months of age, followed by booster doses 12 months after the second dose and at the ages of 6 and 12 years. Although the number of JE cases has markedly decreased after the universal vaccination program, JE predominantly occurs in adults. The aim of this study was to assess the age-specific prevalence of the JE-neutralizing antibody (NTAb) among adolescents and adults in Korea. A total of 1603 specimens were collected from a healthy Korean population above 15 years old in five provinces. The JE-NTAb titers were measured with the pseudotyped virus assay and considered to be positive at ≥ 1:50. The seropositivity of JE-NTAb was the highest in the 15–29 years category (>95%) and gradually began to decrease in the age group of 30–44 years (89.42%). The lowest and second lowest JE-NTAb seropositive rates were observed among those aged 70 years or older (59.77%) and those aged 55–59 years (75.24%), respectively. Subjects from Seoul exhibited the highest JE-NTAb titer in all age groups compared to other provinces. In conclusion, the JE-NTAb seropositive rates and titers have maintained appropriate levels in the general Korean population. We propose that adult immunization and boosters at 12 years of age against JE are not strongly recommended in Korea. Full article

(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)

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18 pages, 640 KiB

Open AccessArticle

Trends, Coverage and Influencing Determinants of Influenza Vaccination in the Elderly: A Population-Based National Survey in Spain (2006–2017)

by Silvia Portero de la Cruz and Jesús Cebrino

Vaccines 2020, 8(2), 327; https://doi.org/10.3390/vaccines8020327 - 19 Jun 2020

Cited by 14 | Viewed by 3381

Abstract

Influenza is a significant public health problem and the elderly are at a greater risk of contracting the disease. The vaccination coverage of the elderly is below the Spanish target of 65% for each influenza season. The aims of this study were to [...] Read more.

Influenza is a significant public health problem and the elderly are at a greater risk of contracting the disease. The vaccination coverage of the elderly is below the Spanish target of 65% for each influenza season. The aims of this study were to report the coverage of influenza vaccination in Spain among the population aged ≥65 years and high-risk groups for suffering chronic diseases, to analyze the time trends from 2006 to 2017 and to identify the factors which affect vaccination coverage. A nationwide cross-sectional study was conducted including 20,753 non-institutionalized individuals aged ≥65 years who had participated in the Spanish National Health Surveys in 2006, 2011/2012, and 2017. Sociodemographic, health-related variables, and influenza vaccination data were used. A logistic regression analysis was performed to determine the variables associated with influenza vaccination. Influenza vaccination coverage was 60%. By chronic condition, older people with high cholesterol levels and cancer had the lowest vaccination coverage (62.41% and 60.73%, respectively). This coverage declined from 2006 to 2017 in both groups. Higher influenza vaccination was associated with males, Spanish nationality, normal social support perceived, polypharmacy, worse perceived health, participation in other preventive measures, and increasing age and the number of chronic diseases. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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21 pages, 5934 KiB

Open AccessArticle

IFN-I Independent Antiviral Immune Response to Vesicular Stomatitis Virus Challenge in Mouse Brain

by Anurag R. Mishra, Siddappa N. Byrareddy and Debasis Nayak

Vaccines 2020, 8(2), 326; https://doi.org/10.3390/vaccines8020326 - 19 Jun 2020

Cited by 7 | Viewed by 4630

Abstract

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role [...] Read more.

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role of IFN-I in the CNS against viral encephalitis is not entirely clear. Here we have implemented the combination of global differential gene expression profiling followed by bioinformatics analysis to decipher the CNS immune response in the presence and absence of the IFN-I signaling. We observed that vesicular stomatitis virus (VSV) infection induced 281 gene changes in wild-type (WT) mice primarily associated with IFN-I signaling. This was accompanied by an increase in antiviral response through leukocyte vascular patrolling and leukocyte influx along with the expression of potent antiviral factors. Surprisingly, in the absence of the IFN-I signaling (IFNAR^−/− mice), a significantly higher (1357) number of genes showed differential expression compared to the WT mice. Critical candidates such as IFN-γ, CCL5, CXCL10, and IRF1, which are responsible for the recruitment of the patrolling leukocytes, are also upregulated in the absence of IFN-I signaling. The computational network analysis suggests the presence of the IFN-I independent pathway that compensates for the lack of IFN-I signaling in the brain. The analysis shows that TNF-α is connected maximally to the networked candidates, thus emerging as a key regulator of gene expression and recruitment of myeloid cells to mount antiviral action. This pathway could potentiate IFN-γ release; thereby, synergistically activating IRF1-dependent ISG expression and antiviral response. Full article

(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)

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14 pages, 265 KiB

Open AccessArticle

Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials

by Alexander Domnich, Ilaria Manini, Donatella Panatto, Giovanna Elisa Calabrò and Emanuele Montomoli

Vaccines 2020, 8(2), 325; https://doi.org/10.3390/vaccines8020325 - 19 Jun 2020

Cited by 13 | Viewed by 2886

Abstract

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe [...] Read more.

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe the patterns of use of the various immunological assays available to measure the influenza vaccine-induced adaptive immune response and to determine its correlates of protection. A total of 76.5% of the studies included in our analysis measured only the humoral immune response. Among these, the hemagglutination-inhibition assay was by far the most widely used. Other, less common, humoral immune response assays were: virus neutralization (21.7%), enzyme-linked immunosorbent (10.1%), single radial hemolysis (4.6%), and assays able to quantify anti-neuraminidase antibodies (1.7%). By contrast, cell-mediated immunity was quantified in only 23.5% of studies. Several variables were significantly associated with the use of single assays. Specifically, some influenza vaccine types (e.g., adjuvanted, live attenuated and cell culture-derived or recombinant), study phase and study sponsorship pattern were usually found to be statistically significant predictors. We discuss the principal findings and make some suggestions from the point of view of the various stakeholders. Full article

(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)

12 pages, 2239 KiB

Open AccessArticle

The Effect of Vaccination with Live Attenuated Neethling Lumpy Skin Disease Vaccine on Milk Production and Mortality—An Analysis of 77 Dairy Farms in Israel

by Michal Morgenstern and Eyal Klement

Vaccines 2020, 8(2), 324; https://doi.org/10.3390/vaccines8020324 - 19 Jun 2020

Cited by 12 | Viewed by 4692

Abstract

Lumpy skin disease (LSD) is an economically important, arthropod borne viral disease of cattle. Vaccination by the live attenuated homologous Neethling vaccine was shown as the most efficient measure for controlling LSD. However, adverse effects due to vaccination were never quantified in a [...] Read more.

Lumpy skin disease (LSD) is an economically important, arthropod borne viral disease of cattle. Vaccination by the live attenuated homologous Neethling vaccine was shown as the most efficient measure for controlling LSD. However, adverse effects due to vaccination were never quantified in a controlled field study. The aim of this study was to quantify the milk production loss and mortality due to vaccination against LSD. Daily milk production, as well as culling and mortality, were retrieved for 21,844 cows accommodated in 77 dairy cattle farms in Israel. Adjusted milk production was calculated for each day during the 30 days post vaccination. This was compared to the preceding month by fitting mixed effects linear models. Culling and mortality rates were compared between the 60 days periods prior and post vaccination, by survival analysis. The results of the models indicate no significant change in milk production during the 30 days post vaccination period. No difference was observed between the pre- and post-vaccination periods in routine culling, as well as in immediate culling and in-farm mortality. We conclude that adverse effects due to Neethling vaccination are negligible. Full article

(This article belongs to the Special Issue Controlled Clinical Evaluation of Veterinary Vaccines)

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14 pages, 5253 KiB

Open AccessArticle

Liver Stiffness Hinders Normalization of Systemic Inflammation and Endothelial Activation after Hepatitis C Virus (HCV) Eradication in HIV/HCV Coinfected Patients

by Beatriz Álvarez, Clara Restrepo, Marcial García, María A. Navarrete-Muñoz, María A. Jiménez-Sousa, Laura Prieto, Alfonso Cabello, Sara Nistal, Salvador Resino, Miguel Górgolas, Norma Rallón and José M. Benito

Vaccines 2020, 8(2), 323; https://doi.org/10.3390/vaccines8020323 - 19 Jun 2020

Cited by 4 | Viewed by 2761

Abstract

Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these [...] Read more.

Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1ß, IL-6, IL-12p70, IL-8, TNFα, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNFα receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p < 0.0001), VCAM-1 (p < 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (≥7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness. Full article

(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)

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9 pages, 348 KiB

Open AccessReview

Livestock and Poultry Production in Nepal and Current Status of Vaccine Development

by Uddab Poudel, Umesh Dahal, Nabin Upadhyaya, Saroj Chaudhari and Santosh Dhakal

Vaccines 2020, 8(2), 322; https://doi.org/10.3390/vaccines8020322 - 19 Jun 2020

Cited by 15 | Viewed by 14247

Abstract

The livestock and poultry sectors are an integral part of Nepalese economy and lifestyle. Livestock and poultry populations have continuously been increasing in the last decade in Nepal and are likely to follow that trend as the interests in this field is growing. [...] Read more.

The livestock and poultry sectors are an integral part of Nepalese economy and lifestyle. Livestock and poultry populations have continuously been increasing in the last decade in Nepal and are likely to follow that trend as the interests in this field is growing. Infectious diseases such as Foot and Mouth Disease (FMD), Peste des Petits Ruminants (PPR), hemorrhagic septicemia (HS), black quarter (BQ), swine fever, avian influenza, and Newcastle disease (ND) constitute one of the major health challenges to the Nepalese livestock and poultry industry. Vaccinations are an efficient means of preventing the occurrence and spread of several diseases in animals and birds. Considering this fact, the government of Nepal began the production of veterinary vaccines in the 1960s. Nepal is self-reliant in producing several vaccines for cattle and buffaloes, sheep and goats, pigs, and poultry. Despite these efforts, the demand for vaccines is not met, especially in the commercial poultry sector, as Nepal spends billions of rupees in vaccine imports each year. There is a need of strengthening laboratory facilities for the isolation and characterization of field strains of pathogens and capacity building for the production of different types of vaccines using the latest technologies to be self-reliant in veterinary vaccine production in the future in Nepal. Full article

(This article belongs to the Section Veterinary Vaccines)

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17 pages, 4355 KiB

Open AccessArticle

Overcoming Tumor Resistance to Oncolyticvaccinia Virus with Anti-PD-1-Based Combination Therapy by Inducing Antitumor Immunity in the Tumor Microenvironment

by So Young Yoo, Narayanasamy Badrinath, Su-Nam Jeong, Hyun Young Woo and Jeong Heo

Vaccines 2020, 8(2), 321; https://doi.org/10.3390/vaccines8020321 - 19 Jun 2020

Cited by 17 | Viewed by 3876

Abstract

The tumor microenvironment (TME) comprises different types of immune cells, which limit the therapeutic efficacy of most drugs. Although oncolytic virotherapy (OVT) boosts antitumor immunity via enhanced infiltration of tumor-infiltrated lymphocytes (TILs), immune checkpoints on the surface of tumors and TILs protect tumor [...] Read more.

The tumor microenvironment (TME) comprises different types of immune cells, which limit the therapeutic efficacy of most drugs. Although oncolytic virotherapy (OVT) boosts antitumor immunity via enhanced infiltration of tumor-infiltrated lymphocytes (TILs), immune checkpoints on the surface of tumors and TILs protect tumor cells from TIL recognition and apoptosis. OVT and immune checkpoint blockade (ICB)-based combination therapy might overcome this issue. Therefore, combination immunotherapies to modify the immunosuppressive nature of TME and block immune checkpoints of immune cells and tumors are considered. In this study, cancer-favoring oncolytic vaccinia virus (CVV) and anti–programmed cell death protein-1 (anti-PD-1) were used to treat mouse colorectal cancer. Weekly-based intratumoral CVV and intraperitoneal anti-PD-1 injections were performed on Balb/c mice with subcutaneous CT26 tumors. Tumor volume, survival curve, and immunohistochemistry-based analysis demonstrated the benefit of co-treatment, especially simultaneous treatment with CVV and anti-PD-1. Infiltration of CD8⁺PD-1⁺ T-cells showed correlation with these results. Splenocytes enumeration also suggested CD4⁺ and CD8⁺ T-cell upregulation. In addition, upregulated CD8, PD-1, and CD86 messenger RNA expression was observed in this combination therapy. Therefore, CVV+anti-PD-1 combination therapy induces antitumor immunity in the TME, overcoming the rigidity and resistance of the TME in refractory cancers. Full article

(This article belongs to the Special Issue Cancer Vaccine)

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4 pages, 192 KiB

Open AccessViewpoint

Merit of an Ursodeoxycholic Acid Clinical Trial in COVID-19 Patients

by Subbaya Subramanian, Tinen Iles, Sayeed Ikramuddin and Clifford J. Steer

Vaccines 2020, 8(2), 320; https://doi.org/10.3390/vaccines8020320 - 19 Jun 2020

Cited by 29 | Viewed by 7614

Abstract

Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized [...] Read more.

Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment”. Bear bile is rich in UDCA, comprising up to 40–50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration. Full article

17 pages, 3169 KiB

Open AccessArticle

Vaccination with Recombinant Subolesin Antigens Provides Cross-Tick Species Protection in Bos indicus and Crossbred Cattle in Uganda

by Paul D. Kasaija, Marinela Contreras, Fredrick Kabi, Swidiq Mugerwa and José de la Fuente

Vaccines 2020, 8(2), 319; https://doi.org/10.3390/vaccines8020319 - 18 Jun 2020

Cited by 29 | Viewed by 3812

Abstract

Cattle tick infestations and transmitted pathogens affect animal health, production and welfare with an impact on cattle industry in tropical and subtropical countries. Anti-tick vaccines constitute an effective and sustainable alternative to the traditional methods for the control of tick infestations. Subolesin (SUB)-based [...] Read more.

Cattle tick infestations and transmitted pathogens affect animal health, production and welfare with an impact on cattle industry in tropical and subtropical countries. Anti-tick vaccines constitute an effective and sustainable alternative to the traditional methods for the control of tick infestations. Subolesin (SUB)-based vaccines have shown efficacy for the control of multiple tick species, but several factors affect the development of new and more effective vaccines for the control of tick infestations. To address this challenge, herein we used a regional and host/tick species driven approach for vaccine design and implementation. The objective of the study was to develop SUB-based vaccines for the control of the most important tick species (Rhipicephalus appendiculatus, R. decoloratus and Amblyomma variegatum) affecting production of common cattle breeds (Bos indicus and B. indicus x B. taurus crossbred) in Uganda. In this way, we addressed the development of anti-tick vaccines as an intervention to prevent the economic losses caused by ticks and tick-borne diseases in the cattle industry in Uganda. The results showed the possibility of using SUB antigens for the control of multiple tick species in B. indicus and crossbred cattle and suggested the use of R. appendiculatus SUB to continue research on vaccine design and formulation for the control of cattle ticks in Uganda. Future directions would include quantum vaccinology approaches based on the characterization of the SUB protective epitopes, modeling of the vaccine E under Ugandan ecological and epidemiological conditions and optimization of vaccine formulation including the possibility of oral administration. Full article

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42 pages, 4917 KiB

Open AccessArticle

Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells

by Juris Jansons, Ekaterina Bayurova, Dace Skrastina, Alisa Kurlanda, Ilze Fridrihsone, Dmitry Kostyushev, Anastasia Kostyusheva, Alexander Artyuhov, Erdem Dashinimaev, Darya Avdoshina, Alla Kondrashova, Vladimir Valuev-Elliston, Oleg Latyshev, Olesja Eliseeva, Stefan Petkov, Maxim Abakumov, Laura Hippe, Irina Kholodnyuk, Elizaveta Starodubova, Tatiana Gorodnicheva, Alexander Ivanov, Ilya Gordeychuk and Maria Isaguliants Show full author list Hide full author list

Vaccines 2020, 8(2), 318; https://doi.org/10.3390/vaccines8020318 - 18 Jun 2020

Cited by 2 | Viewed by 4274

Abstract

Telomerase reverse transcriptase (TERT) is a classic tumor-associated antigen overexpressed in majority of tumors. Several TERT-based cancer vaccines are currently in clinical trials, but immune correlates of their antitumor activity remain largely unknown. Here, we characterized fine specificity and lytic potential of immune [...] Read more.

Telomerase reverse transcriptase (TERT) is a classic tumor-associated antigen overexpressed in majority of tumors. Several TERT-based cancer vaccines are currently in clinical trials, but immune correlates of their antitumor activity remain largely unknown. Here, we characterized fine specificity and lytic potential of immune response against rat TERT in mice. BALB/c mice were primed with plasmids encoding expression-optimized hemagglutinin-tagged or nontagged TERT or empty vector and boosted with same DNA mixed with plasmid encoding firefly luciferase (Luc DNA). Injections were followed by electroporation. Photon emission from booster sites was assessed by in vivo bioluminescent imaging. Two weeks post boost, mice were sacrificed and assessed for IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α) production by T-cells upon their stimulation with TERT peptides and for anti-TERT antibodies. All TERT DNA-immunized mice developed cellular and antibody response against epitopes at the N-terminus and reverse transcriptase domain (rtTERT) of TERT. Photon emission from mice boosted with TERT/TERT-HA+Luc DNA was 100 times lower than from vector+Luc DNA-boosted controls. Bioluminescence loss correlated with percent of IFN-γ/IL-2/TNF-α producing CD8+ and CD4+ T-cells specific to rtTERT, indicating immune clearance of TERT/Luc-coexpressing cells. We made murine adenocarcinoma 4T1luc2 cells to express rtTERT by lentiviral transduction. Expression of rtTERT significantly reduced the capacity of 4T1luc2 to form tumors and metastasize in mice, while not affecting in vitro growth. Mice which rejected the tumors developed T-cell response against rtTERT and low/no response to the autoepitope of TERT. This advances rtTERT as key component of TERT-based therapeutic vaccines against cancer. Full article

(This article belongs to the Special Issue Cancer Immunotherapy: Advances and Future Prospects)

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13 pages, 2847 KiB

Open AccessArticle

PD-1 Immune Checkpoint Blockade Promotes Therapeutic Cancer Vaccine to Eradicate Lung Cancer

by Pournima Kadam and Sherven Sharma

Vaccines 2020, 8(2), 317; https://doi.org/10.3390/vaccines8020317 - 18 Jun 2020

Cited by 18 | Viewed by 3418

Abstract

(1) Background: Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the activation of immune responses against cancer. Therapeutic vaccination, which induces specific immune responses against tumor antigens (Ags), is an attractive option. (2) Methods: Utilizing a K-RasG12Dp53null murine [...] Read more.

(1) Background: Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the activation of immune responses against cancer. Therapeutic vaccination, which induces specific immune responses against tumor antigens (Ags), is an attractive option. (2) Methods: Utilizing a K-RasG12Dp53null murine lung cancer model we determined tumor burden, tumor-infiltrating T cell (TIL) cytolysis, immunohistochemistry, flow cytometry, and CD4 and CD8 depletion to evaluate the efficacy of PD-1 blockade combined with CCL21-DC tumor lysate vaccine. (3) Results: Anti-PD-1 plus CCL21-DC tumor lysate vaccine administered to mice bearing established tumors (150 mm³) increased expression of perforin and granzyme B in the tumor microenvironment (TME), increased tumor-infiltrating T cell (TIL) activity, and caused 80% tumor eradication. Mice with treatment-induced tumor eradication developed immunological memory, enabling tumor rejection upon challenge and cancer-recurrence-free survival. The depletion of CD4 or CD8 abrogated the antitumor activity of combined therapy. PD-1 blockade or CCL21-DC tumor lysate vaccine monotherapy reduced tumor burden without tumor eradication. (4) Conclusion: Immune checkpoint blockade promotes the activity of the therapeutic cancer vaccine. PD-1 blockade plus CCL21-DC tumor lysate vaccine therapy could benefit lung cancer patients. Full article

(This article belongs to the Special Issue Cancer Vaccine)

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17 pages, 1888 KiB

Open AccessArticle

Defining Elimination of Genital Warts—A Modified Delphi Study

by Laila Khawar, Dorothy A. Machalek, David G. Regan, Basil Donovan, Skye McGregor and Rebecca J. Guy

Vaccines 2020, 8(2), 316; https://doi.org/10.3390/vaccines8020316 - 18 Jun 2020

Cited by 1 | Viewed by 3511

Abstract

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW [...] Read more.

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW elimination definition exists. Taking Australia as a case study, we aimed to reach expert consensus on a proposed GW elimination definition using a modified Delphi process. Method: We used modelling and epidemiological data to estimate the expected number of new GW cases, from pre-vaccination (baseline) in 2006 to the year 2060 in Australian heterosexuals, men who have sex with men (MSM), and newly arrived international travellers and migrants. We used these data and the literature, to develop a questionnaire containing ten elimination-related items, each with 9-point Likert scales (1—strongly disagree; 9—strongly agree). The survey was completed by 18 experts who participated in a full day face-to-face modified Delphi study, in which individuals and then small groups discussed and scored each item. The process was repeated online for items where consensus (≥70% agreement) was not initially achieved. Median and coefficient of variation (COV) were used to describe the central tendency and variability of responses, respectively. Findings: There was a 95% participation rate in the face-to-face session, and 84% response rate in the final online round. The median item score ranged between 7.0 and 9.0 and the COV was ≤0.30 on all items. Consensus was reached that at ≥80% HPV vaccination coverage, GW will be eliminated as a public health problem in Australia by 2060. During this time period there will be a 95% reduction in population-level incidence compared with baseline, equivalent to <1 GW case per 10,000 population. The reductions will occur most rapidly in Australian heterosexuals, with 73%, 90% and 97% relative reductions by years 2021, 2030 and 2060, respectively. The proportion of new GW cases attributable to importation will increase from 3.6% in 2006 to ~49% in 2060. Interpretation: Our results indicate that the vaccination programme will minimise new GW cases in the Australian population, but importation of cases will continue. This is the first study to define GW elimination at a national level. The framework developed could be used to define GW elimination in other countries, with thresholds particularly valuable for vaccination programme impact evaluation. Funding: LK supported through an Australian Government Research Training Programme Scholarship; unconditional funding from Seqirus to support the Delphi Workshop. Full article

(This article belongs to the Special Issue Vaccination and Public Health: Optimizing Vaccine Uptake through the Application of Social and Behavioral Science Theory, Principles, and Strategies)

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18 pages, 3400 KiB

Open AccessArticle

ELISA-Based Assay for Studying Major and Minor Group Rhinovirus–Receptor Interactions

by Petra Pazderova, Eva E. Waltl, Verena Niederberger-Leppin, Sabine Flicker, Rudolf Valenta and Katarzyna Niespodziana

Vaccines 2020, 8(2), 315; https://doi.org/10.3390/vaccines8020315 - 18 Jun 2020

Cited by 4 | Viewed by 3705

Abstract

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, [...] Read more.

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, and the need for preclinical models for the screening of vaccine candidates and antiviral compounds. We report the establishment and characterization of an ELISA-based assay for studying major and minor group RV–receptor interactions. This assay is based on the interaction of purified virus with plate-bound human receptor proteins, intercellular adhesion molecule 1 (ICAM-1), and low density lipoprotein receptor (LDLR). Using RV strain-specific antibodies, we demonstrate the specific binding of a panel of major and minor RV group types including RV-A and RV-B strains to ICAM-1 and LDLR, respectively. We show that the RV–receptor interaction can be blocked with receptor-specific antibodies as well as with soluble receptors and neutralizing RV-specific antibodies. The assay is more sensitive than a cell culture-based virus neutralization test. The ELISA assay will therefore be useful for the preclinical evaluation for preventive and therapeutic strategies targeting the RV–receptor interaction, such as vaccines, antibodies, and anti-viral compounds. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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14 pages, 2348 KiB

Open AccessArticle

Search of Potential Vaccine Candidates against Trueperella pyogenes Infections through Proteomic and Bioinformatic Analysis

by Ángela Galán-Relaño, Lidia Gómez-Gascón, Antonio Rodríguez-Franco, Inmaculada Luque, Belén Huerta, Carmen Tarradas and Manuel J. Rodríguez-Ortega

Vaccines 2020, 8(2), 314; https://doi.org/10.3390/vaccines8020314 - 17 Jun 2020

Cited by 7 | Viewed by 2387

Abstract

Trueperella pyogenes is an opportunistic pathogen, responsible for important infections in pigs and significant economic losses in swine production. To date, there are no available commercial vaccines to control diseases caused by this bacterium. In this work, we performed a comparative proteomic analysis [...] Read more.

Trueperella pyogenes is an opportunistic pathogen, responsible for important infections in pigs and significant economic losses in swine production. To date, there are no available commercial vaccines to control diseases caused by this bacterium. In this work, we performed a comparative proteomic analysis of 15 T. pyogenes clinical isolates, by “shaving” live cells, followed by LC-MS/MS, aiming at the identification of the whole set of surface proteins (i.e., the “pan-surfome”) as a source of antigens to be tested in further studies as putative vaccine candidates, or used in diagnostic tools. A total of 140 surface proteins were detected, comprising 25 cell wall proteins, 10 secreted proteins, 23 lipoproteins and 82 membrane proteins. After describing the “pan-surfome”, the identified proteins were ranked in three different groups based on the following criteria: to be (i) surface-exposed, (ii) highly conserved and (iii) widely distributed among different isolates. Two cell wall proteins, three lipoproteins, four secreted and seven membrane proteins were identified in more than 70% of the studied strains, were highly expressed and highly conserved. These proteins are potential candidates, alone or in combination, to obtain effective vaccines against T. pyogenes or to be used in the diagnosis of this pathogen. Full article

(This article belongs to the Special Issue Omics and Bioinformatics Approaches to Identify Novel Antigens for Vaccine Investigation and Development)

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24 pages, 696 KiB

Open AccessReview

Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

by Daniel Sepulveda-Crespo, Salvador Resino and Isidoro Martinez

Vaccines 2020, 8(2), 313; https://doi.org/10.3390/vaccines8020313 - 17 Jun 2020

Cited by 14 | Viewed by 3700

Abstract

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the [...] Read more.

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant. Full article

(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)

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16 pages, 447 KiB

Open AccessReview

The African Swine Fever Virus (ASFV) Topoisomerase II as a Target for Viral Prevention and Control

by João Coelho and Alexandre Leitão

Vaccines 2020, 8(2), 312; https://doi.org/10.3390/vaccines8020312 - 17 Jun 2020

Cited by 14 | Viewed by 4223

Abstract

African swine fever (ASF) is, once more, spreading throughout the world. After its recent reintroduction in Georgia, it quickly reached many neighboring countries in Eastern Europe. It was also detected in Asia, infecting China, the world’s biggest pig producer, and spreading to many [...] Read more.

African swine fever (ASF) is, once more, spreading throughout the world. After its recent reintroduction in Georgia, it quickly reached many neighboring countries in Eastern Europe. It was also detected in Asia, infecting China, the world’s biggest pig producer, and spreading to many of the surrounding countries. Without any vaccine or effective treatment currently available, new strategies for the control of the disease are mandatory. Its etiological agent, the African swine fever virus (ASFV), has been shown to code for a type II DNA topoisomerase. These are enzymes capable of modulating the topology of DNA molecules, known to be essential in unicellular and multicellular organisms, and constitute targets in antibacterial and anti-cancer treatments. In this review, we summarize most of what is known about this viral enzyme, pP1192R, and discuss about its possible role(s) during infection. Given the essential role of type II topoisomerases in cells, the data so far suggest that pP1192R is likely to be equally essential for the virus and thus a promising target for the elaboration of a replication-defective virus, which could provide the basis for an effective vaccine. Furthermore, the use of inhibitors could be considered to control the spread of the infection during outbreaks and therefore limit the spreading of the disease. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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26 pages, 5576 KiB

Open AccessArticle

Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis

by John Davis Coakley, Eamon P. Breen, Ana Moreno-Olivera, Alhanouf I. Al-Harbi, Ashanty M. Melo, Brian O’Connell, Ross McManus, Derek G. Doherty and Thomas Ryan

Vaccines 2020, 8(2), 311; https://doi.org/10.3390/vaccines8020311 - 17 Jun 2020

Cited by 6 | Viewed by 3329

Abstract

Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy [...] Read more.

Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA⁺, CD197⁺), central memory (CD45RA⁻, CD197⁺), effector memory (CD45RA⁻, CD197⁻), or terminally differentiated (CD45RA⁺, CD197⁻). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA⁺, CD27⁺), central memory (CD45RA⁻, CD27⁺), effector memory (CD45RA⁻, CD27⁻), or terminally differentiated (CD45RA⁺, CD27⁻). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis. Full article

(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)

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Vaccines, Volume 8, Issue 2 (June 2020) – 196 articles

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