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Vaccines
Volume 7
Issue 4
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Vaccines, Volume 7, Issue 4 (December 2019) – 96 articles

Cover Story (view full-size image): A novel semisynthetic archaeosome formulation, sulfated S-lactosylarchaeol (SLA), has strong immunostimulatory activity for the induction of antigen-specific immunity following systemic immunization. We evaluated SLA archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral and cellular responses to those generated with mimetics of commercial adjuvants. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, the simple admixed SLA archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells, producing multiple cytokines. View this paper
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11 pages, 459 KiB  
Review
Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice
by Christian Münz
Vaccines 2019, 7(4), 217; https://doi.org/10.3390/vaccines7040217 - 17 Dec 2019
Cited by 5 | Viewed by 4492
Abstract
Mice with reconstituted human immune system components (humanized mice) offer the unique opportunity to test vaccines preclinically in the context of vaccine adjuvant sensing by human antigen presenting cells and priming of human cytotoxic lymphocyte populations. These features are particularly attractive for immune [...] Read more.
Mice with reconstituted human immune system components (humanized mice) offer the unique opportunity to test vaccines preclinically in the context of vaccine adjuvant sensing by human antigen presenting cells and priming of human cytotoxic lymphocyte populations. These features are particularly attractive for immune control of the Epstein–Barr virus (EBV), which represents the most potent growth-transforming pathogen in man and exclusively relies on cytotoxic lymphocytes for its asymptomatic persistence in the vast majority of healthy virus carriers. This immune control is particularly impressive because EBV infects more than 95% of the human adult population and persists without pathology for more than 50 years in most of them. This review will discuss the pathologies that EBV elicits in humanized mice, which immune responses control it in this model, as well as which passive and active vaccination schemes with adoptive T cell transfer and with virus-like particles or individual antigens, respectively, have been explored in this model so far. EBV-specific CD8+ T cell priming in humanized mice could provide crucial insights into how cytotoxic lymphocytes against other viruses and tumors might be elicited by vaccination in humans. Full article
(This article belongs to the Special Issue Humanized Mice in Vaccinology: Opportunities and Challenges)
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28 pages, 9552 KiB  
Article
Polyamine Transport Protein PotD Protects Mice against Haemophilus parasuis and Elevates the Secretion of Pro-Inflammatory Cytokines of Macrophage via JNK–MAPK and NF–κB Signal Pathways through TLR4
by Ke Dai, Xiaoyu Ma, Zhen Yang, Yung-Fu Chang, Sanjie Cao, Qin Zhao, Xiaobo Huang, Rui Wu, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Xintian Wen and Yiping Wen
Vaccines 2019, 7(4), 216; https://doi.org/10.3390/vaccines7040216 - 14 Dec 2019
Cited by 9 | Viewed by 3276
Abstract
The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and [...] Read more.
The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and cellular immune responses and elevate lymphocyte proliferation, thus eliciting a Th1-type immune response in a murine immunity and infection model. Stimulation of Raw 264.7 macrophages with PotD validated that Toll-like receptor 4, rather than 2, participated in the positive transcription and expression of pro-inflammatory cytokines IL–1β, IL–6, and TNF–α using qPCR and ELISA. Blocking signal-regulated JNK–MAPK and RelA(p65) pathways significantly decreased PotD-induced pro-inflammatory cytokine production. Overall, we conclude that vaccination of PotD could induce both humoral and cellular immune responses and provide immunoprotection against H. parasuis challenge. The data also suggest that Glaesserella PotD is a novel pro-inflammatory mediator and induces TLR4-dependent pro-inflammatory activity in Raw 264.7 macrophages through JNK–MAPK and RelA(p65) pathways. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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26 pages, 1204 KiB  
Article
Mapping Host-Related Correlates of Influenza Vaccine-Induced Immune Response: An Umbrella Review of the Available Systematic Reviews and Meta-Analyses
by Alexander Domnich, Ilaria Manini, Giovanna Elisa Calabrò, Chiara de Waure and Emanuele Montomoli
Vaccines 2019, 7(4), 215; https://doi.org/10.3390/vaccines7040215 - 13 Dec 2019
Cited by 15 | Viewed by 3796
Abstract
Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza [...] Read more.
Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus- and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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5 pages, 195 KiB  
Article
Evaluation of Immunity to Measles in a Cohort of Medical Students in Rome, Italy
by Luca Coppeta, Giorgia Biondi, Piergiorgio Lieto and Antonio Pietroiusti
Vaccines 2019, 7(4), 214; https://doi.org/10.3390/vaccines7040214 - 13 Dec 2019
Cited by 9 | Viewed by 2329
Abstract
Background: Measles is a highly contagious viral disease with serious complications. Currently, in Italy, measles vaccination is not mandatory for health care workers (HCWs) and medical students, and the free offer of the Measles Mumps Rubella (MMR) vaccine is the only national prevention [...] Read more.
Background: Measles is a highly contagious viral disease with serious complications. Currently, in Italy, measles vaccination is not mandatory for health care workers (HCWs) and medical students, and the free offer of the Measles Mumps Rubella (MMR) vaccine is the only national prevention measure to increase the coverage rate among these subjects. Aims: The aim of our study was to evaluate the impact on vaccination rate of the National Plan of Vaccine Prevention (NPVP) implemented in 2017. Material and Methods: This is a retrospective observational study that evaluated the measles-specific IgG immunity status of medical students at the University Tor Vergata of Rome, which underwent occupational health surveillance from 1 January to 31 December 2018. Results: In 2018, 84 of 319 students (26.30%) were serologically non-immune to measles; among these, 16 (19%) had previously been vaccinated, and 35 of the remaining 68 students accepted the MMR vaccine. Therefore, 33 out of 319 students did not undergo vaccination in 2018. These data are similar to those obtained in the previous year. In the 2017 screening, 84/314 (26.75%) students tested negative at the serological screening, whereas 15/85 (17.8%) among them documented a previous vaccination with two doses of the MMR vaccine; 69 students tested as unprotected. Vaccine compliance was 51.44%. Conclusions: No change in vaccination coverage occurred after the introduction of the last NPVP. Further efforts are needed to sensitize target populations about the relevance of vaccination; providing pre-employment screening for measles and free vaccine might be useful for this purpose. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
20 pages, 3519 KiB  
Article
Protective Immunity against Canine Distemper Virus in Dogs Induced by Intranasal Immunization with a Recombinant Probiotic Expressing the Viral H Protein
by Yanping Jiang, Shuo Jia, Dianzhong Zheng, Fengsai Li, Shengwen Wang, Li Wang, Xinyuan Qiao, Wen Cui, Lijie Tang, Yigang Xu, Xianzhu Xia and Yijing Li
Vaccines 2019, 7(4), 213; https://doi.org/10.3390/vaccines7040213 - 10 Dec 2019
Cited by 10 | Viewed by 4791
Abstract
Canine distemper virus (CDV) elicits a severe contagious disease in a broad range of hosts. CDV mortality rates are 50% in domestic dogs and 100% in ferrets. Its primary infection sites are respiratory and intestinal mucosa. This study aimed to develop an effective [...] Read more.
Canine distemper virus (CDV) elicits a severe contagious disease in a broad range of hosts. CDV mortality rates are 50% in domestic dogs and 100% in ferrets. Its primary infection sites are respiratory and intestinal mucosa. This study aimed to develop an effective mucosal CDV vaccine using a non-antibiotic marked probiotic pPGΔCm-T7g10-EGFP-H/L. casei 393 strain expressing the CDV H protein. Its immunogenicity in BALB/c mice was evaluated using intranasal and oral vaccinations, whereas in dogs the intranasal route was used for vaccination. Our results indicate that this probiotic vaccine can stimulate a high level of secretory immunoglobulin A (sIgA)-based mucosal and IgG-based humoral immune responses in mice. SIgA levels in the nasal lavage and lungs were significantly higher in intranasally vaccinated mice than those in orally vaccinated mice. Both antigen-specific IgG and sIgA antibodies were effectively elicited in dogs through the intranasal route and demonstrated superior immunogenicity. The immune protection efficacy of the probiotic vaccine was evaluated by challenging the immunized dogs with virulent CDV 42 days after primary immunization. Dogs of the pPGΔCm-T7g10-EGFP-H/L. casei 393 group were completely protected against CDV. The proposed probiotic vaccine could be promising for protection against CDV infection in dogs. Full article
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22 pages, 4071 KiB  
Article
Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment
by Idoia Buldain, Aize Pellon, Beñat Zaldibar, Aitziber Antoran, Leire Martin-Souto, Leire Aparicio-Fernandez, Maialen Areitio, Emilio Mayayo, Aitor Rementeria, Fernando L. Hernando and Andoni Ramirez-Garcia
Vaccines 2019, 7(4), 212; https://doi.org/10.3390/vaccines7040212 - 10 Dec 2019
Cited by 10 | Viewed by 3408
Abstract
The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies [...] Read more.
The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines. 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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11 pages, 941 KiB  
Article
Parenteral–Oral Immunization with Plant-Derived HBcAg as a Potential Therapeutic Vaccine against Chronic Hepatitis B
by Marcin Pyrski, Adam Aron Mieloch, Adam Plewiński, Aneta Basińska-Barczak, Aleksandra Gryciuk, Piotr Bociąg, Marek Murias, Jakub Dalibor Rybka and Tomasz Pniewski
Vaccines 2019, 7(4), 211; https://doi.org/10.3390/vaccines7040211 - 09 Dec 2019
Cited by 10 | Viewed by 3196
Abstract
Chronic hepatitis B (CHB) is the cause of severe liver damage, cirrhosis, and hepatocellular carcinoma for over 240 million people worldwide. Nowadays, several types of treatment are being investigated, including immunotherapy using hepatitis B core antigen (HBcAg) assembled into highly immunogenic capsid-like particles [...] Read more.
Chronic hepatitis B (CHB) is the cause of severe liver damage, cirrhosis, and hepatocellular carcinoma for over 240 million people worldwide. Nowadays, several types of treatment are being investigated, including immunotherapy using hepatitis B core antigen (HBcAg) assembled into highly immunogenic capsid-like particles (CLPs). Immunogenicity of plant-produced and purified HBcAg, administered parenterally or intranasally, was previously reported. In this study, a novel parenteral–oral vaccination scheme is proposed using plant-derived HBcAg preparations. The antigen for injection was obtained via transient expression in Nicotiana benthamiana. HBcAg-producing transgenic lettuce was lyophilized and used as an orally delivered booster. The intracellular location of plant-produced HBcAg CLPs implies additional protection in the digestive tract during oral immunization. BALB/c mice were intramuscularly primed with 10 µg of the purified antigen and orally boosted twice with 5 or 200 ng of HBcAg. A long-lasting and significant systemic response after boosting with 200 ng HBcAg was induced, with anti-HBc titer of 25,000. Concomitantly, an insignificant mucosal response was observed, with an S-IgA titer of only 500. The profile of IgG isotypes indicates a predominant Th1 type of immune response, supplemented by Th2, after injection–oral vaccination. The results demonstrate that a low dose of parenteral–oral immunization with plant-derived HBcAg can elicit a specific and efficient response. This study presents a potential new pathway of CHB treatment. Full article
(This article belongs to the Section Therapeutic Vaccines and Antibody Therapeutics)
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13 pages, 1762 KiB  
Article
Anti-Idiotype Vaccine Provides Protective Immunity Against Vibrio Harveyi in Grouper (Epinephelus Coioides)
by Wan-Ling Huang, Shu-Chun Chuang and Chung-Da Yang
Vaccines 2019, 7(4), 210; https://doi.org/10.3390/vaccines7040210 - 09 Dec 2019
Cited by 6 | Viewed by 3269
Abstract
Since anti-idiotype antibodies (anti-Id Abs) can display internal images similar to the epitopes of the original antigens, we aimed to produce an effective vaccine based on anti-Id Abs to protect grouper from Vibrio harveyi. Anti-Id IgG showing V. harveyi-like internal images [...] Read more.
Since anti-idiotype antibodies (anti-Id Abs) can display internal images similar to the epitopes of the original antigens, we aimed to produce an effective vaccine based on anti-Id Abs to protect grouper from Vibrio harveyi. Anti-Id IgG showing V. harveyi-like internal images was produced from rabbits immunized with the Id portion of grouper anti-V. harveyi antibodies and its Fab portion, anti-Id IgG (Fab), was then prepared to use as the anti-Id vaccine. The resulting anti-Id IgG (Fab) was intraperitoneally injected twice at a 21-day interval into grouper to evaluate its ability to induce effective anti-V. harveyi immunity and protection, in comparison with inactivated V. harveyi bacteria. We found that administration of grouper with anti-Id IgG (Fab) resulted in enhanced V. harveyi-specific serum titers, as well as lymphocyte proliferation. In addition, three weeks after boosting, 90% (18/20) of fish immunized with anti-Id IgG (Fab) survived at least 28 days after a lethal challenge of the heterologous, virulent strain of V. harveyi. The capability of this anti-Id IgG (Fab) to imitate the epitopes of V. harveyi antigens and effectively induce protective immunity would be advantageous for its application in developing an efficacious vaccine against V. harveyi for future farm use in fish. Full article
(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)
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13 pages, 1634 KiB  
Article
Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix
by Wesley de Jong, Lorna Leal, Jozefien Buyze, Pieter Pannus, Alberto Guardo, Maria Salgado, Beatriz Mothe, Jose Molto, Sara Moron-Lopez, Cristina Gálvez, Eric Florence, Guido Vanham, Eric van Gorp, Christian Brander, Sabine Allard, Kris Thielemans, Javier Martinez-Picado, Montserrat Plana, Felipe García and Rob A. Gruters
Vaccines 2019, 7(4), 209; https://doi.org/10.3390/vaccines7040209 - 06 Dec 2019
Cited by 26 | Viewed by 5343
Abstract
Therapeutic vaccinations aim to re-educate human immunodeficiency virus (HIV)-1-specific immune responses to achieve durable control of HIV-1 replication in virally suppressed infected individuals after antiretroviral therapy (ART) is interrupted. In a double blinded, placebo-controlled phase IIa multicenter study, we investigated the safety and [...] Read more.
Therapeutic vaccinations aim to re-educate human immunodeficiency virus (HIV)-1-specific immune responses to achieve durable control of HIV-1 replication in virally suppressed infected individuals after antiretroviral therapy (ART) is interrupted. In a double blinded, placebo-controlled phase IIa multicenter study, we investigated the safety and immunogenicity of intranodal administration of the HIVACAT T cell Immunogen (HTI)-TriMix vaccine. It consists of naked mRNA based on cytotoxic T lymphocyte (CTL) targets of subdominant and conserved HIV-1 regions (HTI), in combination with mRNAs encoding constitutively active TLR4, the ligand for CD40 and CD70 as adjuvants (TriMix). We recruited HIV-1-infected individuals under stable ART. Study-arms HTI-TriMix, TriMix or Water for Injection were assigned in an 8:3:3 ratio. Participants received three vaccinations at weeks 0, 2, and 4 in an inguinal lymph node. Two weeks after the last vaccination, immunogenicity was evaluated using ELISpot assay. ART was interrupted at week 6 to study the effect of the vaccine on viral rebound. The vaccine was considered safe and well tolerated. Eighteen percent (n = 37) of the AEs were considered definitely related to the study product (grade 1 or 2). Three SAEs occurred: two were unrelated to the study product, and one was possibly related to ART interruption (ATI). ELISpot assays to detect T cell responses using peptides covering the HTI sequence showed no significant differences in immunogenicity between groups. There were no significant differences in viral load rebound dynamics after ATI between groups. The vaccine was safe and well tolerated. We were not able to demonstrate immunogenic effects of the vaccine. Full article
(This article belongs to the Section HIV Vaccines)
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22 pages, 3196 KiB  
Article
An MVA Vector Expressing HIV-1 Envelope under the Control of a Potent Vaccinia Virus Promoter as a Promising Strategy in HIV/AIDS Vaccine Design
by Patricia Pérez, María Q. Marín, Adrián Lázaro-Frías, Carlos Óscar S. Sorzano, Mauro Di Pilato, Carmen E. Gómez, Mariano Esteban and Juan García-Arriaza
Vaccines 2019, 7(4), 208; https://doi.org/10.3390/vaccines7040208 - 06 Dec 2019
Cited by 5 | Viewed by 4318
Abstract
Highly attenuated poxviral vectors, such as modified vaccinia virus ankara (MVA), are promising vaccine candidates against several infectious diseases. One of the approaches developed to enhance the immunogenicity of poxvirus vectors is increasing the promoter strength and accelerating during infection production levels of [...] Read more.
Highly attenuated poxviral vectors, such as modified vaccinia virus ankara (MVA), are promising vaccine candidates against several infectious diseases. One of the approaches developed to enhance the immunogenicity of poxvirus vectors is increasing the promoter strength and accelerating during infection production levels of heterologous antigens. Here, we have generated and characterized the biology and immunogenicity of an optimized MVA-based vaccine candidate against HIV/AIDS expressing HIV-1 clade B gp120 protein under the control of a novel synthetic late/early optimized (LEO) promoter (LEO160 promoter; with a spacer length of 160 nucleotides), termed MVA-LEO160-gp120. In infected cells, MVA-LEO160-gp120 significantly increased the expression levels of HIV-1 gp120 mRNA and protein, compared to the clinical vaccine MVA-B vector expressing HIV-1 gp120 under the control of the commonly used synthetic early/late promoter. When mice were immunized with a heterologous DNA-prime/MVA-boost protocol, the immunization group DNA-gp120/MVA-LEO160-gp120 induced an enhancement in the magnitude of gp120-specific CD4+ and CD8+ T-cell responses, compared to DNA-gp120/MVA-B; with most of the responses being mediated by the CD8+ T-cell compartment, with a T effector memory phenotype. DNA-gp120/MVA-LEO160-gp120 also elicited a trend to a higher magnitude of gp120-specific CD4+ T follicular helper cells, and modest enhanced levels of antibodies against HIV-1 gp120. These findings revealed that this new optimized vaccinia virus promoter could be considered a promising strategy in HIV/AIDS vaccine design, confirming the importance of early expression of heterologous antigen and its impact on the antigen-specific immunogenicity elicited by poxvirus-based vectors. Full article
(This article belongs to the Special Issue HIV Vaccine)
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15 pages, 1829 KiB  
Article
Simultaneous Deletion of Virulence Factors and Insertion of Antigens into the Infectious Laryngotracheitis Virus Using NHEJ-CRISPR/Cas9 and Cre–Lox System for Construction of a Stable Vaccine Vector
by Mustafa Ozan Atasoy, Mohammed A. Rohaim and Muhammad Munir
Vaccines 2019, 7(4), 207; https://doi.org/10.3390/vaccines7040207 - 05 Dec 2019
Cited by 23 | Viewed by 5147
Abstract
Infectious laryngotracheitis virus (ILTV) is a promising vaccine vector due to its heterologous gene accommodation capabilities, low pathogenicity, and potential to induce cellular and humoral arms of immunity. Owing to these characteristics, different gene-deletion versions of ILTVs have been successfully deployed as a [...] Read more.
Infectious laryngotracheitis virus (ILTV) is a promising vaccine vector due to its heterologous gene accommodation capabilities, low pathogenicity, and potential to induce cellular and humoral arms of immunity. Owing to these characteristics, different gene-deletion versions of ILTVs have been successfully deployed as a vector platform for the development of recombinant vaccines against multiple avian viruses using conventional recombination methods, which are tedious, time-demanding, and error-prone. Here, we applied a versatile, and customisable clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 accompanied with Cre–Lox system to simultaneously delete virulence factors and to insert foreign genes in the ILTV genome. Using this pipeline, we successfully deleted thymidine kinase (TK) and unique short 4 (US4) genes and inserted fusion (F) gene of the Newcastle disease virus without adversely affecting ILTV replication and expression of the F protein. Taken together, the proposed approach offers novel tools to attenuate (by deletion of virulence factor) and to generate multivalent (by insertion of heterologous genes) vaccine vectors to protect chickens against pathogens of poultry and public health importance. Full article
(This article belongs to the Special Issue Herpesvirus Vaccines)
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10 pages, 1358 KiB  
Article
Yellow Fever Virus Genotyping Tool and Investigation of Suspected Adverse Events Following Yellow Fever Vaccination
by Izabela Maurício de Rezende, Pedro Augusto Alves, Matheus Soares Arruda, Andreza Parreiras Gonçalves, Gabriela Fernanda Garcia Oliveira, Leonardo Soares Pereira, Maria Rita Teixeira Dutra, Ana Carolina Campi-Azevedo, Valéria Valim, Renata Tourinho, Jaquelline Germano de Oliveira, Carlos Eduardo Calzavara, Rodrigo Fabiano do Carmo Said, Erna Geessien Kroon, Olindo Assis Martins-Filho, Andrea Teixeira-Carvalho and Betânia Paiva Drumond
Vaccines 2019, 7(4), 206; https://doi.org/10.3390/vaccines7040206 - 04 Dec 2019
Cited by 5 | Viewed by 3416
Abstract
The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years [...] Read more.
The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5′UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes. Full article
(This article belongs to the Special Issue Arbovirus Vaccines That Circulate within the Same Ecological Niche: Zika, Dengue & Chikungunya)
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28 pages, 5474 KiB  
Article
The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice
by Marilynn J. Culbreth, Sergei S. Biryukov, Jennifer L. Shoe, Jennifer L. Dankmeyer, Melissa Hunter, Christopher P. Klimko, Raysa Rosario-Acevedo, David P. Fetterer, Alicia M. Moreau, Susan L. Welkos and Christopher K. Cote
Vaccines 2019, 7(4), 205; https://doi.org/10.3390/vaccines7040205 - 03 Dec 2019
Cited by 5 | Viewed by 4924
Abstract
The administration of antipyretic analgesics prior to, in conjunction with, or due to sequelae associated with vaccination is a common yet somewhat controversial practice. In the context of human vaccination, it is unclear if even short-term analgesic regimens can significantly alter the resulting [...] Read more.
The administration of antipyretic analgesics prior to, in conjunction with, or due to sequelae associated with vaccination is a common yet somewhat controversial practice. In the context of human vaccination, it is unclear if even short-term analgesic regimens can significantly alter the resulting immune response, as literature exists to support several scenarios including substantial immune interference. In this report, we used a live attenuated Yersinia pestis vaccine to examine the impact of analgesic administration on the immune response elicited by a single dose of a live bacterial vaccine in mice. Mice were assessed by evaluating natural and provoked behavior, as well as food and water consumption. The resulting immune responses were assessed by determining antibody titers against multiple antigens and assaying cellular responses in stimulated splenocytes collected from vaccinated animals. We observed no substantial benefit to the mice associated with the analgesic administration. Splenocytes from both C57BL/6 and BALB/c vaccinated mice receiving acetaminophen have a significantly reduced interferon-gamma (IFN-γ) recall response. Additionally, there is a significantly lower immunoglobulin (Ig)G2a/IgG1 ratio in vaccinated BALB/c mice treated with either acetaminophen or meloxicam and a significantly lower IgG2c/IgG1 ratio in vaccinated C57BL/6 mice treated with acetaminophen. Taken together, our data indicate that the use of analgesics, while possibly ethically warranted, may hinder the accurate characterization and evaluation of novel vaccine strategies with little to no appreciable benefits to the vaccinated mice. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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16 pages, 1598 KiB  
Article
Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins
by Bassel Akache, Lise Deschatelets, Blair A. Harrison, Renu Dudani, Felicity C. Stark, Yimei Jia, Amir Landi, John L. M. Law, Michael Logan, Darren Hockman, Juthika Kundu, D. Lorne Tyrrell, Lakshmi Krishnan, Michael Houghton and Michael J. McCluskie
Vaccines 2019, 7(4), 204; https://doi.org/10.3390/vaccines7040204 - 03 Dec 2019
Cited by 22 | Viewed by 4460
Abstract
Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a [...] Read more.
Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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20 pages, 985 KiB  
Review
Considering Genomic and Immunological Correlates of Protection for a Dengue Intervention
by Joshua Blight, Eduardo Alves and Arturo Reyes-Sandoval
Vaccines 2019, 7(4), 203; https://doi.org/10.3390/vaccines7040203 - 03 Dec 2019
Cited by 2 | Viewed by 3833
Abstract
Over three billion are at risk of dengue infection with more than 100 million a year presenting with symptoms that can lead to deadly haemorrhagic disease. There are however no treatments available and the only licensed vaccine shows limited efficacy and is able [...] Read more.
Over three billion are at risk of dengue infection with more than 100 million a year presenting with symptoms that can lead to deadly haemorrhagic disease. There are however no treatments available and the only licensed vaccine shows limited efficacy and is able to enhance the disease in some cases. These failures have mainly been due to the complex pathology and lack of understanding of the correlates of protection for dengue virus (DENV) infection. With increasing data suggesting both a protective and detrimental effect for antibodies and CD8 T-cells whilst having complex environmental dynamics. This review discusses the roles of genomic and immunological aspects of DENV infection, providing both a historical interpretation and fresh discussion on how this information can be used for the next generation of dengue interventions. Full article
(This article belongs to the Special Issue Arbovirus Vaccines That Circulate within the Same Ecological Niche: Zika, Dengue & Chikungunya)
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13 pages, 2235 KiB  
Article
Evaluation of the Safety and Protection Efficacy of spiC and nmpC or rfaL Deletion Mutants of Salmonella Enteritidis as Live Vaccine Candidates for Poultry Non-Typhoidal Salmonellosis
by Qiuchun Li, Yue Zhu, Jingwei Ren, Zhuang Qiao, Chao Yin, Honghong Xian, Yu Yuan, Shizhong Geng and Xinan Jiao
Vaccines 2019, 7(4), 202; https://doi.org/10.3390/vaccines7040202 - 30 Nov 2019
Cited by 8 | Viewed by 3331
Abstract
Salmonella enterica serovar Enteritidis (S. Enteritidis) is a host-ranged pathogen that can infect both animals and humans. Poultry and poultry products are the main carriers of S. Enteritidis, which can be transmitted to humans through the food chain. To eradicate the prevalence [...] Read more.
Salmonella enterica serovar Enteritidis (S. Enteritidis) is a host-ranged pathogen that can infect both animals and humans. Poultry and poultry products are the main carriers of S. Enteritidis, which can be transmitted to humans through the food chain. To eradicate the prevalence of S. Enteritidis in poultry farms, it is necessary to develop novel vaccines against the pathogen. In this study, we constructed two vaccine candidates, CZ14-1∆spiC∆nmpC and CZ14-1∆spiC∆rfaL, and evaluated their protective efficacy. Both mutant strains were much less virulent than the parental strain, as determined by the 50% lethal dose (LD50) for three-day-old specific-pathogen free (SPF) White Leghorns and Hyline White chickens. Immunization with the mutant candidates induced highly specific humoral immune responses and expression of cytokines IFN-γ, IL-1β, and IL-6. In addition, the mutant strains were found to be persistent for almost three weeks post-infection. The survival percentages of chickens immunized with CZ14-1∆spiC∆nmpC and CZ14-1∆spiC∆rfaL reached 80% and 75%, respectively, after challenge with the parental strain. Overall, these results demonstrate that the two mutant strains can be developed as live attenuated vaccines. Full article
(This article belongs to the Section Veterinary Vaccines)
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15 pages, 276 KiB  
Article
Assessing Vaccine Hesitancy among Healthcare Workers: A Cross-Sectional Study at an Italian Paediatric Hospital and the Development of a Healthcare Worker’s Vaccination Compliance Index
by Sonia Paoli, Chiara Lorini, Francesco Puggelli, Antonino Sala, Maddalena Grazzini, Diana Paolini, Paolo Bonanni and Guglielmo Bonaccorsi
Vaccines 2019, 7(4), 201; https://doi.org/10.3390/vaccines7040201 - 29 Nov 2019
Cited by 30 | Viewed by 5078
Abstract
Healthcare workers (HCWs) in paediatric hospitals are an important source of advice on vaccinations, but vaccine hesitancy can affect even these professionals. The aim of this study is to assess this phenomenon, measuring it by means of a scoring system. A survey was [...] Read more.
Healthcare workers (HCWs) in paediatric hospitals are an important source of advice on vaccinations, but vaccine hesitancy can affect even these professionals. The aim of this study is to assess this phenomenon, measuring it by means of a scoring system. A survey was conducted in five departments of an Italian paediatric university hospital of national interest. Vaccination against influenza was considered a behavioral indicator of vaccination uptake. Using the collected data, the healthcare worker’s vaccination compliance index (HVCI) was computed. The results demonstrate statistically significant differences between departments and professional profiles. Nearly 80% of the sample was not immunized against seasonal influenza. According to the HVCI scores, the most hesitant departments are the intensive care unit, emergency room, and oncohematology department, while the most hesitant professional profiles are nurses and auxiliary staff. The score of the unvaccinated is significantly lower than that of the vaccinated, and the same difference was found between those who self-perceive to be skilled versus unskilled. The HVCI score was statistically verified as a predictive parameter to assess vaccination against seasonal influenza. By means of strategic training policies, both HVCI and perceived skills could be improved, suggesting that hospital management should draw a complex intervention program to fight against hesitancy. Full article
(This article belongs to the Special Issue Infectious Diseases and Vaccinations in Healthcare Professionals)
13 pages, 780 KiB  
Article
Selective Persistence of HPV Cross-Neutralising Antibodies following Reduced-Dose HPV Vaccine Schedules
by Zheng Quan Toh, Jennie Kosasih, Fiona M. Russell, Rita Reyburn, James Fong, Evelyn Tuivaga, Felisita T. Ratu, Cattram D. Nguyen, Silivia Matanitobua, Lien Anh Ha Do, Trevelyan Menheniott, Ian H. Frazer, Suzanne M. Garland, Edward Kim Mulholland and Paul V. Licciardi
Vaccines 2019, 7(4), 200; https://doi.org/10.3390/vaccines7040200 - 28 Nov 2019
Cited by 7 | Viewed by 3583
Abstract
The duration of cross-neutralising antibody responses (cross-NAb) following HPV immunisation is unknown. We compared cross-NAb responses in cohort of girls who were either unimmunised or had received immunisation with one, two or three doses of 4vHPV (Gardasil®, Merck Inc., Kenilworth, NJ, [...] Read more.
The duration of cross-neutralising antibody responses (cross-NAb) following HPV immunisation is unknown. We compared cross-NAb responses in cohort of girls who were either unimmunised or had received immunisation with one, two or three doses of 4vHPV (Gardasil®, Merck Inc., Kenilworth, NJ, USA) six years earlier, before and one month after a booster dose of 2vHPV (Cervarix®, GSK, Brentford, UK). NAb to potentially cross-reactive HPV genotypes 31, 33, 45, 52 and 58 were measured using a HPV pseudovirion-based neutralisation assay. Girls who had previously received at least one dose of 4vHPV had significantly higher NAb titres for HPV31 when compared with unimmunised girls, whereas no difference in NAb titre was observed for four other genotypes (33, 45, 52 and 58). Following a single further immunisation with 2vHPV, NAb titres to each of the five tested HPV genotypes were comparable for girls who previously received one, two or three doses of 4vHPV, and were significantly higher than for previously unimmunised girls. Immunisation with one, two or three doses of 4vHPV induced NAb to HPV31 that persisted for six years, but there was no persistence of NAb to HPV33, 45, 52 or 58. Our results suggest that one or two doses of 4vHPV may provide long-term protection against HPV31. Full article
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16 pages, 2662 KiB  
Article
Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting
by Monia Pacenti, Nataskya Maione, Enrico Lavezzo, Elisa Franchin, Federico Dal Bello, Lorena Gottardello and Luisa Barzon
Vaccines 2019, 7(4), 199; https://doi.org/10.3390/vaccines7040199 - 28 Nov 2019
Cited by 13 | Viewed by 5453
Abstract
Despite efforts to improve surveillance and vaccination coverage, measles virus (MeV) continues to cause outbreaks also in high-income countries. As the reference laboratory of the Veneto Region, Italy, we analyzed changes in population immunity, described measles outbreaks, investigated MeV genetic diversity, and evaluated [...] Read more.
Despite efforts to improve surveillance and vaccination coverage, measles virus (MeV) continues to cause outbreaks also in high-income countries. As the reference laboratory of the Veneto Region, Italy, we analyzed changes in population immunity, described measles outbreaks, investigated MeV genetic diversity, and evaluated cross-protection of measles vaccination against MeV epidemic strains. Like most European areas, the Veneto Region has suboptimal measles vaccination coverage and is facing a growing public mistrust of vaccination. A progressive decline of measles vaccine uptake was observed during the last decade in the Veneto Region, leading to immunity gaps in children and young adults. Measles outbreaks were caused by the same MeV genotype B3, D4, and D8 strains that were circulating in other European countries. Eleven cases of measles were observed in immunized subjects. These cases were not associated with particular MeV genotypes nor with mutations in epitopes recognized by neutralizing antibodies. Accordingly, sera from fully vaccinated subjects cross-neutralized epidemic MeV strains, including the genotypes B3, D4, and D8, with the same high efficiency demonstrated against the vaccine strain. In fully vaccinated subjects, high MeV IgG antibody titers persisted up to 30 years following vaccination. These results support the use of the current measles-containing vaccines and strategies to strengthen vaccination. Full article
(This article belongs to the Special Issue Vaccination and Vaccine Effectiveness)
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17 pages, 2118 KiB  
Article
Palm Tocotrienol-Adjuvanted Dendritic Cells Decrease Expression of the SATB1 Gene in Murine Breast Cancer Cells and Tissues
by Sitti Rahma Abdul Hafid and Ammu Kutty Radhakrishnan
Vaccines 2019, 7(4), 198; https://doi.org/10.3390/vaccines7040198 - 27 Nov 2019
Cited by 7 | Viewed by 3343
Abstract
The aim of this study was to evaluate the effectiveness of immunotherapy using dendritic cells (DC) pulsed with tumor lysate (a DC vaccine) in combination with daily supplementation of tocotrienol-rich fraction (TRF) to potentiate anti-tumor immune responses. We had previously reported that DC-vaccine [...] Read more.
The aim of this study was to evaluate the effectiveness of immunotherapy using dendritic cells (DC) pulsed with tumor lysate (a DC vaccine) in combination with daily supplementation of tocotrienol-rich fraction (TRF) to potentiate anti-tumor immune responses. We had previously reported that DC-vaccine immunotherapy together with TRF supplementation induced protective immunity to tumor challenge. Breast cancer was induced in female BALB/c mice. The mice were randomly assigned into the treatment groups. At autopsy, peripheral blood was collected in heparinized tube and the expression of cell surface molecules (CD40, CD80, CD83, and CD86) that are crucial for T-cell activation and survival were analyzed by flow cytometry. Tumor was excised from each animal and snap-frozen. Total RNA was extracted from each tumor tissue for microarray and gene expression analysis. Total protein was extracted from tumor tissue for protein expression studies using Western blotting. The results show that systemic administration of 1 mg TRF daily in combination with DC-vaccine immunotherapy (DC + TL + TRF) caused a marked reduction (p < 0.05) of tumor size and increased (p < 0.05) the survival rates of the tumor-inoculated mice. The expression of CD40, CD80, CD83, and CD86 were upregulated in peripheral blood from the DC + TL + TRF group compared to other groups. In addition, there was higher expression of FasL in tumor-excised mice from the DC + TL + TRF group compared to other groups. FasL plays an important role in maintaining immune privilege and is required for cytotoxic T-lymphocyte (CTL) activity. Microarray analysis identified several genes involved in the regulation of cancer. In this study, we focused on the special AT rich binding protein 1 (SATB1) gene, which was reported to have dual functions, one of which was to induce aggressive growth in breast cancer cells. Tumors from DC + TL + TRF mice showed lower (p < 0.05) expression of SATB1 gene. Further study will be conducted to investigate the molecular functions of and the role of SATB1 in 4T1 mammary cancer cells and DC. In conclusion, TRF supplementation can potentiate the effectiveness of DC-vaccine immunotherapy. 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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19 pages, 3032 KiB  
Article
miR29a and miR378b Influence CpG-Stimulated Dendritic Cells and Regulate cGAS/STING Pathway
by Abid Ullah Shah, Yanan Cao, Naila Siddique, Jian Lin and Qian Yang
Vaccines 2019, 7(4), 197; https://doi.org/10.3390/vaccines7040197 - 26 Nov 2019
Cited by 13 | Viewed by 4174
Abstract
The Cytosine–phosphate–guanosine (CpG) motif, which is specifically recognized intracellularly by dendritic cells (DCs), plays a crucial role in regulating the innate immune response. MicroRNAs (miRNAs) can strongly influence the antigen-presenting ability of DCs. In this study, we examine the action of miRNAs on [...] Read more.
The Cytosine–phosphate–guanosine (CpG) motif, which is specifically recognized intracellularly by dendritic cells (DCs), plays a crucial role in regulating the innate immune response. MicroRNAs (miRNAs) can strongly influence the antigen-presenting ability of DCs. In this study, we examine the action of miRNAs on CpG-stimulated and control DCs, as well as their effect on cyclic guanosine monophosphate-adenosine monophosphate (GMP–AMP) synthase (cGAS) and the stimulator of interferon genes (STING) signal pathway. Firstly, we selected miRNAs (miR-29a and miR-378b) based on expression in CpG-stimulated mouse bone marrow-derived dendritic cells (BMDCs). Secondly, we investigated the functions of miR-29a and miR-378b on CpG-stimulated and unstimulated BMDCs. The results showed that miR-29a and miR-378b increased expression of both the immunoregulatory DC surface markers (CD86 and CD40) and the immunosuppressive molecule CD273 by DCs. Thirdly, cytokine detection revealed that both miR-29a and miR-378b enhanced interferon-β (IFN-β) expression while suppressing tumor necrosis factor-α (TNF-α) production. Finally, our results suggest that miR-378b can bind TANK-binding kinase binding protein 1 (TBKBP1) to activate the cGAS/STING signaling pathway. By contrast, miR-29a targeted interferon regulatory factor 7 (IRF7) and promoted the expression of STING. Together, our results provide insight into the molecular mechanism of miRNA induction by CpG to regulate DC function. Full article
(This article belongs to the Section Veterinary Vaccines)
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21 pages, 1666 KiB  
Article
Deletion of Two Genes in Burkholderia pseudomallei MSHR668 That Target Essential Amino Acids Protect Acutely Infected BALB/c Mice and Promote Long Term Survival
by Kei Amemiya, Jennifer L. Dankmeyer, Sergei S. Biryukov, Sylvia R. Treviño, Christopher P. Klimko, Sherry M. Mou, David P. Fetterer, Preston G. Garnes, Christopher K. Cote, Patricia L. Worsham and David DeShazer
Vaccines 2019, 7(4), 196; https://doi.org/10.3390/vaccines7040196 - 26 Nov 2019
Cited by 14 | Viewed by 2995
Abstract
Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen Burkholderia pseudomallei. It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine [...] Read more.
Melioidosis is an emerging disease that is caused by the facultative intracellular pathogen Burkholderia pseudomallei. It is intrinsically resistant to many antibiotics and host risk factors play a major role in susceptibility to infection. Currently, there is no human or animal vaccine against melioidosis. In this study, multiple B. pseudomallei MSHR668 deletion mutants were evaluated as live attenuated vaccines in the sensitive BALB/c mouse model of melioidosis. The most efficacious vaccines after an intraperitoneal challenge with 50-fold over the 50% median lethal dose (MLD50) with B. pseudomallei K96243 were 668 ΔhisF and 668 ΔilvI. Both vaccines completely protected mice in the acute phase of infection and showed significant protection (50% survivors) during the chronic phase of infection. The spleens of the survivors that were examined were sterile. Splenocytes from mice vaccinated with 668 ΔhisF and 668 ΔilvI expressed higher amounts of IFN-γ after stimulation with B. pseudomallei antigens than splenocytes from mice vaccinated with less protective candidates. Finally, we demonstrate that 668 ΔhisF is nonlethal in immunocompromised NOD/SCID mice. Our results show that 668 ΔhisF and 668 ΔilvI provide protective cell-mediated immune responses in the acute phase of infection and promote long term survival in the sensitive BALB/c mouse model of melioidosis. Full article
(This article belongs to the Section Vaccines against (re)emerging and Tropical Infections Diseases)
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17 pages, 2438 KiB  
Article
Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice
by Brigette N. Corder, Brianna L. Bullard, Jennifer L. DeBeauchamp, Natalia A. Ilyushina, Richard J. Webby and Eric A. Weaver
Vaccines 2019, 7(4), 195; https://doi.org/10.3390/vaccines7040195 - 23 Nov 2019
Cited by 10 | Viewed by 3821
Abstract
Annually, influenza A virus (IAV) infects ~5–10% of adults and 20–30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of [...] Read more.
Annually, influenza A virus (IAV) infects ~5–10% of adults and 20–30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of IAV are needed. Here we developed and tested a novel mosaic H1 HA immunogen. The mosaic immunogen was optimized in silico to include the most potential B and T cell epitopes (PBTE) across a diverse population of human H1 IAV. Phylogenetic analysis showed that the mosaic HA localizes towards the non-pandemic 2009 strains which encompasses the broadest diversity in the H1 IAV population. We compared the mosaic H1 immunogen to wild-type HA immunogens and the commercial inactivated influenza vaccine, Fluzone. When analyzed by ELISA, the mosaic immunogen induced stronger antibody responses against all four diverse H1 HA proteins. When analyzing T cell responses, again the mosaic immunogen induced stronger cellular immunity against all 4 diverse HA strains. Not only was the magnitude of T cell responses strongest in mosaic immunized mice, the number of epitopes recognized was also greater. The mosaic vaccinated mice showed strong cross-protection against challenges with three divergent IAV strains. These data show that the mosaic immunogen induces strong cross-protective immunity and should be investigated further as a universal influenza vaccine. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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14 pages, 1186 KiB  
Review
Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion
by Ruth M. Ruprecht, Bishal Marasini and Rajesh Thippeshappa
Vaccines 2019, 7(4), 194; https://doi.org/10.3390/vaccines7040194 - 23 Nov 2019
Cited by 17 | Viewed by 4302
Abstract
The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of different Ig classes in rhesus macaques [...] Read more.
The power of mucosal anti-HIV-1 envelope immunoglobulins (Igs) to block virus transmission is underappreciated. We used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. We mucosally instilled recombinant neutralizing monoclonal antibodies (nmAbs) of different Ig classes in rhesus macaques (RMs) followed by mucosal simian–human immunodeficiency virus (SHIV) challenge. We gave anti-HIV-1 IgM, IgG, and dimeric IgA (dIgA) versions of the same human nmAb, HGN194 that targets the conserved V3 loop crown. Surprisingly, dIgA1 with its wide-open, flat hinge protected 83% of the RMs against intrarectal R5-tropic SHIV-1157ipEL-p challenge, whereas dIgA2, with its narrow hinge, only protected 17% of the animals—despite identical epitope specificities and in vitro neutralization curves of the two dIgA isotypes (Watkins et al., AIDS 2013 27(9):F13-20). These data imply that factors in addition to neutralization determine in vivo protection. We propose that this underlying protective mechanism is immune exclusion, which involves large nmAb/virion aggregates that prevent virus penetration of mucosal barriers. Future studies need to find biomarkers that predict effective immune exclusion in vivo. Vaccine development strategies against HIV-1 and/or other mucosally transmissible pathogens should include induction of strong mucosal Abs of different Ig classes to defend epithelial barriers against pathogen invasion. Full article
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
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16 pages, 1771 KiB  
Article
Highly Pathogenic Avian Influenza H5 Hemagglutinin Fused with the A Subunit of Type IIb Escherichia coli Heat Labile Enterotoxin Elicited Protective Immunity and Neutralization by Intranasal Immunization in Mouse and Chicken Models
by Neos Tang, Shi-Wei Lin, Ting-Hsuan Chen, Jia-Tsrong Jan, Hung-Yi Wu and Suh-Chin Wu
Vaccines 2019, 7(4), 193; https://doi.org/10.3390/vaccines7040193 - 22 Nov 2019
Cited by 2 | Viewed by 3101
Abstract
Highly pathogenic avian influenza viruses are classified by the World Organization for Animal Health (OIE) as causes of devastating avian diseases. This study aimed to develop type IIb Escherichia coli heat-labile enterotoxin (LTIIb) as novel mucosal adjuvants for mucosal vaccine development. The fusion [...] Read more.
Highly pathogenic avian influenza viruses are classified by the World Organization for Animal Health (OIE) as causes of devastating avian diseases. This study aimed to develop type IIb Escherichia coli heat-labile enterotoxin (LTIIb) as novel mucosal adjuvants for mucosal vaccine development. The fusion protein of H5 and LTIIb-A subunit was expressed and purified for mouse and chicken intranasal immunizations. Intranasal immunization with the H5-LTIIb-A fusion protein in mice elicited potent neutralizing antibodies in sera and bronchoalveolar lavage fluids, induced stronger Th1 and Th17 cellular responses in spleen and cervical lymph nodes, and improved protection against H5N1 influenza virus challenge. More interestingly, intranasal immunization with the H5-LTIIb-A fusion protein in chickens elicited high titers of IgY, IgA, hemagglutinin inhibition (HAI), and neutralizing antibodies in their antisera. This study employed the novel adjuvants of LTIIb for the development of a new generation of mucosal vaccines against highly pathogenic avian influenza viruses. Full article
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11 pages, 2189 KiB  
Article
Application of HDR-CRISPR/Cas9 and Erythrocyte Binding for Rapid Generation of Recombinant Turkey Herpesvirus-Vectored Avian Influenza Virus Vaccines
by Pengxiang Chang, Faisal Ameen, Joshua E. Sealy, Jean-Remy Sadeyen, Sushant Bhat, Yongqing Li and Munir Iqbal
Vaccines 2019, 7(4), 192; https://doi.org/10.3390/vaccines7040192 - 22 Nov 2019
Cited by 19 | Viewed by 7167
Abstract
Avian influenza viruses (AIVs) are highly contagious and have caused huge economical loss to the poultry industry. AIV vaccines remain one of the most effective methods of controlling this disease. Turkey herpesvirus (HVT) is a commonly used live attenuated vaccine against Marek’s disease; [...] Read more.
Avian influenza viruses (AIVs) are highly contagious and have caused huge economical loss to the poultry industry. AIV vaccines remain one of the most effective methods of controlling this disease. Turkey herpesvirus (HVT) is a commonly used live attenuated vaccine against Marek’s disease; it has also been used as a viral vector for recombinant AIV vaccine development. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system is a gene editing tool which, in vaccinology, has facilitated the development of recombinant DNA viral-vectored vaccines. Here, we utilize homology-directed repair (HDR) for the generation of a HVT–H7N9 HA bivalent vaccine; a H7N9 HA expression cassette was inserted into the intergenic region between UL45 and UL46 of HVT. To optimize the selection efficiency of our bivalent vaccine, we combined CRISPR/Cas9 with erythrocyte binding to rapidly generate recombinant HVT–H7HA candidate vaccines. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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15 pages, 1486 KiB  
Article
Feasibility of Using a Luminescence-Based Method to Determine Serum Bactericidal Activity against Neisseria gonorrhoeae
by Fiona Clow, Conor J O’Hanlon, Myron Christodoulides and Fiona J Radcliff
Vaccines 2019, 7(4), 191; https://doi.org/10.3390/vaccines7040191 - 21 Nov 2019
Cited by 5 | Viewed by 2857
Abstract
Development of a vaccine to limit the impact of antibiotic resistant Neisseria gonorrhoeae is now a global priority. Serum bactericidal antibody (SBA) is a possible indicator of protective immunity to N. gonorrhoeae, but conventional assays measure colony forming units (CFU), which is [...] Read more.
Development of a vaccine to limit the impact of antibiotic resistant Neisseria gonorrhoeae is now a global priority. Serum bactericidal antibody (SBA) is a possible indicator of protective immunity to N. gonorrhoeae, but conventional assays measure colony forming units (CFU), which is time-consuming. A luminescent assay that quantifies ATP as a surrogate measure of bacterial viability was tested on N. gonorrhoeae strains FA1090, MS11 and P9-17 and compared to CFU-based readouts. There was a linear relationship between CFU and ATP levels for all three strains (r > 0.9). Normal human serum (NHS) is a common source of complement for SBA assays, but needs to be screened for non-specific bactericidal activity. NHS from 10 individuals were used for serum sensitivity assays—sensitivity values were significantly reduced with the ATP method for FA1090 (5/10, p < 0.05) and MS11 (10/10, p < 0.05), whereas P9-17 data were comparable for all donors. Our results suggest that measuring ATP underestimates serum sensitivity of N. gonorrhoeae and that the CFU method is a better approach. However, mouse anti-P9-17 outer membrane vesicles (OMV) SBA titres to P9-17 were comparable with both methods (r = 0.97), suggesting this assay can be used to rapidly screen sera for bactericidal antibodies to gonococci. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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17 pages, 3615 KiB  
Article
A Vaccinology Approach to the Identification and Characterization of Dermanyssus gallinae Candidate Protective Antigens for the Control of Poultry Red Mite Infestations
by José Francisco Lima-Barbero, Marinela Contreras, Lourdes Mateos-Hernández, Francisco Manuel Mata-Lorenzo, Roxana Triguero-Ocaña, Olivier Sparagano, Robert D. Finn, Christina Strube, Daniel R.G. Price, Francesca Nunn, Kathryn Bartley, Ursula Höfle, Mariana Boadella, Alasdair J. Nisbet, José de la Fuente and Margarita Villar
Vaccines 2019, 7(4), 190; https://doi.org/10.3390/vaccines7040190 - 20 Nov 2019
Cited by 15 | Viewed by 4102
Abstract
The poultry red mite (PRM), Dermanyssus gallinae, is a hematophagous ectoparasite considered as the major pest in the egg-laying industry. Its pesticide-based control is only partially successful and requires the development of new control interventions such as vaccines. In this study, we [...] Read more.
The poultry red mite (PRM), Dermanyssus gallinae, is a hematophagous ectoparasite considered as the major pest in the egg-laying industry. Its pesticide-based control is only partially successful and requires the development of new control interventions such as vaccines. In this study, we follow a vaccinology approach to identify PRM candidate protective antigens. Based on proteomic data from fed and unfed nymph and adult mites, we selected a novel PRM protein, calumenin (Deg-CALU), which is tested as a vaccine candidate on an on-hen trial. Rhipicephalus microplus Subolesin (Rhm-SUB) was chosen as a positive control. Deg-CALU and Rhm-SUB reduced the mite oviposition by 35 and 44%, respectively. These results support Deg-CALU and Rhm-SUB as candidate protective antigens for the PRM control. Full article
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13 pages, 2134 KiB  
Article
Efficient Delivery of Dengue Virus Subunit Vaccines to the Skin by Microprojection Arrays
by David A. Muller, Alexandra C. I. Depelsenaire, Ashleigh E. Shannon, Daniel Watterson, Simon R. Corrie, Nick S. Owens, Christiana Agyei-Yeboah, Stacey T. M. Cheung, Jin Zhang, Germain J. P. Fernando, Mark A. F. Kendall and Paul R. Young
Vaccines 2019, 7(4), 189; https://doi.org/10.3390/vaccines7040189 - 20 Nov 2019
Cited by 26 | Viewed by 3866
Abstract
Dengue virus is the most important arbovirus impacting global human health, with an estimated 390 million infections annually, and over half the world’s population at risk of infection. While significant efforts have been made to develop effective vaccines to mitigate this threat, the [...] Read more.
Dengue virus is the most important arbovirus impacting global human health, with an estimated 390 million infections annually, and over half the world’s population at risk of infection. While significant efforts have been made to develop effective vaccines to mitigate this threat, the task has proven extremely challenging, with new approaches continually being sought. The majority of protective, neutralizing antibodies induced during infection are targeted by the envelope (E) protein, making it an ideal candidate for a subunit vaccine approach. Using truncated, recombinant, secreted E proteins (sE) of all 4 dengue virus serotypes, we have assessed their immunogenicity and protective efficacy in mice, with or without Quil-A as an adjuvant, and delivered via micropatch array (MPA) to the skin in comparison with more traditional routes of immunization. The micropatch contains an ultra-high density array (21,000/cm2) of 110 μm microprojections. Mice received 3 doses of 1 μg (nanopatch, intradermal, subcutaneous, or intra muscular injection) or 10 μg (intradermal, subcutaneous, or intra muscular injection) of tetravalent sE spaced 4 weeks apart. When adjuvanted with Quil-A, tetravalent sE vaccination delivered via MPA resulted in earlier induction of virus-neutralizing IgG antibodies for all four serotypes when compared with all of the other vaccination routes. Using the infectious dengue virus AG129 mouse infectious dengue model, these neutralizing antibodies protected all mice from lethal dengue virus type 2 D220 challenge, with protected animals showing no signs of disease or circulating virus. If these results can be translated to humans, MPA-delivered sE represents a promising approach to dengue virus vaccination. Full article
(This article belongs to the Special Issue Current Flavivirus Research Important for Vaccine Development )
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Article
Trends in Socioeconomic Inequalities in Full Vaccination Coverage among Vietnamese Children Aged 12–23 Months, 2000–2014: Evidence for Mitigating Disparities in Vaccination
by Hoang-Long Vo, Le-Thai-Bao Huynh, Hao Nguyen Si Anh, Dang-An Do, Thi-Ngoc-Ha Doan, Thi-Huyen-Trang Nguyen and Huy Nguyen Van
Vaccines 2019, 7(4), 188; https://doi.org/10.3390/vaccines7040188 - 18 Nov 2019
Cited by 5 | Viewed by 4882
Abstract
There has been no report on the situation of socioeconomic inequalities in the full vaccination coverage among Vietnamese children. This study aims to assess the trends and changes in the socioeconomic inequalities in the full vaccination coverage among Vietnamese children aged 12–23 months [...] Read more.
There has been no report on the situation of socioeconomic inequalities in the full vaccination coverage among Vietnamese children. This study aims to assess the trends and changes in the socioeconomic inequalities in the full vaccination coverage among Vietnamese children aged 12–23 months from 2000 to 2014. Data were drawn from Multiple Indicator Cluster Surveys (2000, 2006, 2011, and 2014). Concentration index (CCI) and concentration curve (CC) were applied to quantify the degree of the socioeconomic inequalities in full immunization coverage. The prevalence of children fully receiving recommended vaccines was significantly improved during 2000–2014, yet, was still not being covered. The total CCI of full vaccination coverage gradually decreased from 2000 to 2014 (CCI: from 0.241 to 0.009). The CC increasingly became close to the equality line through the survey period, indicating the increasingly narrow gap in child full immunization amongst the poor and the rich. Vietnam witnessed a sharp decrease in socioeconomic inequality in the full vaccination coverage for over a decade. The next policies towards children from vulnerable populations (ethnic minority groups, living in rural areas, and having a mother with low education) belonging to lower socioeconomic groups may mitigate socioeconomic inequalities in full vaccination coverage. Full article
(This article belongs to the Special Issue Infectious Diseases and Vaccinations in Healthcare Professionals)
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