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Vaccines, Volume 5, Issue 3 (September 2017) – 15 articles

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1446 KiB  
Review
Host Transcriptional Response to Ebola Virus Infection
by Emily Speranza and John H Connor
Vaccines 2017, 5(3), 30; https://doi.org/10.3390/vaccines5030030 - 20 Sep 2017
Cited by 18 | Viewed by 7344
Abstract
Ebola virus disease (EVD) is a serious illness that causes severe disease in humans and non-human primates (NHPs) and has mortality rates up to 90%. EVD is caused by the Ebolavirus and currently there are no licensed therapeutics or vaccines to treat EVD. [...] Read more.
Ebola virus disease (EVD) is a serious illness that causes severe disease in humans and non-human primates (NHPs) and has mortality rates up to 90%. EVD is caused by the Ebolavirus and currently there are no licensed therapeutics or vaccines to treat EVD. Due to its high mortality rates and potential as a bioterrorist weapon, a better understanding of the disease is of high priority. Multiparametric analysis techniques allow for a more complete understanding of a disease and the host response. Analysis of RNA species present in a sample can lead to a greater understanding of activation or suppression of different states of the immune response. Transcriptomic analyses such as microarrays and RNA-Sequencing (RNA-Seq) have been important tools to better understand the global gene expression response to EVD. In this review, we outline the current knowledge gained by transcriptomic analysis of EVD. Full article
(This article belongs to the Special Issue Host Responses to Viral Infection)
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Review
Current Status of Rift Valley Fever Vaccine Development
by Bonto Faburay, Angelle Desiree LaBeaud, D. Scott McVey, William C. Wilson and Juergen A. Richt
Vaccines 2017, 5(3), 29; https://doi.org/10.3390/vaccines5030029 - 19 Sep 2017
Cited by 96 | Viewed by 12176
Abstract
Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The [...] Read more.
Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease. Full article
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Article
Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment
by Erika S. Hue, Eric A. Richard, Christine I. Fortier, Guillaume D. Fortier, Romain Paillot, Rudiger Raue and Stéphane L. Pronost
Vaccines 2017, 5(3), 28; https://doi.org/10.3390/vaccines5030028 - 19 Sep 2017
Cited by 8 | Viewed by 4856
Abstract
Equine herpesviruses (EHV) infect horses early during life and the persistence of these viruses through establishment of latency represents a real risk. A better understanding of the immune response to EHV infection is necessary to improve our methods of prevention and decrease the [...] Read more.
Equine herpesviruses (EHV) infect horses early during life and the persistence of these viruses through establishment of latency represents a real risk. A better understanding of the immune response to EHV infection is necessary to improve our methods of prevention and decrease the risk of transmission. The objectives of this study were to characterise the cytokine gene expression profile of peripheral blood mononuclear cells (PBMC) after in vitro EHV-1, EHV-4, and EHV-2 infection and to determine the efficacy of inactivated Parapoxvirus ovis (iPPVO) against these 3 viruses. PBMC were isolated from 3 horses and infected in vitro with EHV-1, EHV-4, or EHV-2 in the presence or absence of iPPVO. In vitro culture of PBMC with EHV-1, EHV-4, and iPPVO induced a significant increase of IFN-α, IFN-β, and IFN-γ gene expression. EHV-4 also triggered a significant increase of IL-6 and TNF-α mRNA. EHV-2 triggered a significant increase of IFN-α, IFN-β, IFN-γ, IL-1β, IL-6, and TNF-α mRNA. The presence of iPPVO induced an earlier and stronger expression of IFN-α, IFN-β, and IFN-γ mRNA during EHV infection and reduced the inflammatory response induced by EHV-2. In conclusion, this study suggests that the presence of iPPVO potentiates the development of the immune response to in vitro EHV infection. Full article
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Article
Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities
by Peter Mastrangelo, Michael J. Norris, Wenming Duan, Edward G. Barrett, Theo J. Moraes and Richard G. Hegele
Vaccines 2017, 5(3), 27; https://doi.org/10.3390/vaccines5030027 - 19 Sep 2017
Cited by 10 | Viewed by 6974
Abstract
Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in [...] Read more.
Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target. Full article
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Case Report
An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine
by Robert H. Wauters, Camellia L. Hernandez and Maureen M. Petersen
Vaccines 2017, 5(3), 26; https://doi.org/10.3390/vaccines5030026 - 19 Sep 2017
Cited by 1 | Viewed by 12416
Abstract
Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We [...] Read more.
Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation. Full article
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Review
A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections
by Mackenzie Henderson, Amanda Bragg, Germin Fahim, Monica Shah and Evelyn R. Hermes-DeSantis
Vaccines 2017, 5(3), 25; https://doi.org/10.3390/vaccines5030025 - 02 Sep 2017
Cited by 29 | Viewed by 6249
Abstract
This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the [...] Read more.
This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, Clostridium difficile, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of Clostridium difficile toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating C. difficile toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines. Full article
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Review
Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection
by Ana Maria Ortega-Prieto and Marcus Dorner
Vaccines 2017, 5(3), 24; https://doi.org/10.3390/vaccines5030024 - 01 Sep 2017
Cited by 48 | Viewed by 11905
Abstract
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, [...] Read more.
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host. Whereas HCV utilizes a cloak-and-dagger approach, disguising itself as a lipid-like particle and immediately crippling essential pattern-recognition pathways, HBV has long been considered a “stealth” virus, due to the complete absence of innate immune responses during infection. Recent developments and access to improved model systems, however, revealed that even though it is among the smallest human-tropic viruses, HBV may, in addition to evading host responses, employ subtle immune evasion mechanisms directed at ensuring viral persistence in the absence of host responses. In this review, we compare the different strategies of both viruses to ensure viral persistence by actively interfering with viral recognition and innate immune responses. Full article
(This article belongs to the Special Issue Host Responses to Viral Infection)
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3593 KiB  
Review
The TRIMendous Role of TRIMs in Virus–Host Interactions
by Sarah Van Tol, Adam Hage, Maria Isabel Giraldo, Preeti Bharaj and Ricardo Rajsbaum
Vaccines 2017, 5(3), 23; https://doi.org/10.3390/vaccines5030023 - 22 Aug 2017
Cited by 99 | Viewed by 13421
Abstract
The innate antiviral response is integral in protecting the host against virus infection. Many proteins regulate these signaling pathways including ubiquitin enzymes. The ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes work together to link ubiquitin, a small protein, onto other ubiquitin molecules [...] Read more.
The innate antiviral response is integral in protecting the host against virus infection. Many proteins regulate these signaling pathways including ubiquitin enzymes. The ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes work together to link ubiquitin, a small protein, onto other ubiquitin molecules or target proteins to mediate various effector functions. The tripartite motif (TRIM) protein family is a group of E3 ligases implicated in the regulation of a variety of cellular functions including cell cycle progression, autophagy, and innate immunity. Many antiviral signaling pathways, including type-I interferon and NF-κB, are TRIM-regulated, thus influencing the course of infection. Additionally, several TRIMs directly restrict viral replication either through proteasome-mediated degradation of viral proteins or by interfering with different steps of the viral replication cycle. In addition, new studies suggest that TRIMs can exert their effector functions via the synthesis of unconventional polyubiquitin chains, including unanchored (non-covalently attached) polyubiquitin chains. TRIM-conferred viral inhibition has selected for viruses that encode direct and indirect TRIM antagonists. Furthermore, new evidence suggests that the same antagonists encoded by viruses may hijack TRIM proteins to directly promote virus replication. Here, we describe numerous virus–TRIM interactions and novel roles of TRIMs during virus infections. Full article
(This article belongs to the Special Issue Host Responses to Viral Infection)
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Article
Challenges in Estimating Vaccine Coverage in Refugee and Displaced Populations: Results From Household Surveys in Jordan and Lebanon
by Timothy Roberton, William Weiss, The Jordan Health Access Study Team, The Lebanon Health Access Study Team and Shannon Doocy
Vaccines 2017, 5(3), 22; https://doi.org/10.3390/vaccines5030022 - 12 Aug 2017
Cited by 31 | Viewed by 6837
Abstract
Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and [...] Read more.
Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and Lebanon, outside of camps, using a mix of random and respondent-driven sampling, to measure coverage of all vaccinations included in the host country’s vaccine schedule. We analyzed the results with a critical eye to data limitations and implications for similar studies. Among households with a child aged 12–23 months, 55.1% of respondents in Jordan and 46.6% in Lebanon were able to produce the child’s EPI card. Only 24.5% of Syrian refugee children in Jordan and 12.5% in Lebanon were fully immunized through routine vaccination services (having received from non-campaign sources: measles, polio 1–3, and DPT 1–3 in Jordan and Lebanon, and BCG in Jordan). Respondents in Jordan (33.5%) and Lebanon (40.1%) reported difficulties obtaining child vaccinations. Our estimated immunization rates were lower than expected and raise serious concerns about gaps in vaccine coverage among Syrian refugees. Although our estimates likely under-represent true coverage, given the additional benefit of campaigns (not captured in our surveys), there is a clear need to increase awareness, accessibility, and uptake of immunization services. Current methods to measure vaccine coverage in refugee and displaced populations have limitations. To better understand health needs in such groups, we need research on: validity of recall methods, links between campaigns and routine immunization programs, and improved sampling of hard-to-reach populations. Full article
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4117 KiB  
Article
Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
by Gabriela Tapia-Calle, Maaike Stoel, Jacqueline De Vries-Idema and Anke Huckriede
Vaccines 2017, 5(3), 21; https://doi.org/10.3390/vaccines5030021 - 09 Aug 2017
Cited by 12 | Viewed by 6865
Abstract
Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system [...] Read more.
Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans. Full article
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Review
Maternal Immunization: New Perspectives on Its Application Against Non-Infectious Related Diseases in Newborns
by Federica Riccardo, Aline Réal, Claudia Voena, Roberto Chiarle, Federica Cavallo and Giuseppina Barutello
Vaccines 2017, 5(3), 20; https://doi.org/10.3390/vaccines5030020 - 01 Aug 2017
Cited by 6 | Viewed by 6406
Abstract
The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection [...] Read more.
The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection against various life-threatening diseases in pregnant women and their children. A number of studies to improve prevention rates and expand protection against the largest possible number of infections are still in progress. The complex unicity of the mother-infant interaction, both during and after pregnancy and which involves immune system cells and molecules, is an able partner in the success of maternal immunization, as intended thus far. Interestingly, new studies have shed light on the versatility of maternal immunization in protecting infants from non-infectious related diseases, such as allergy, asthma and congenital metabolic disorders. However, barely any attempt at applying maternal immunization to the prevention of childhood cancer has been made. The most promising study reported in this new field is a recent proof of concept on the efficacy of maternal immunization in protecting cancer-prone offspring against mammary tumor progression. New investigations into the possibility of exploiting maternal immunization to prevent the onset and/or progression of neuroblastoma, one of the most common childhood malignancies, are therefore justified. Maternal immunization is presented in a new guise in this review. Attention will be focused on its versatility and potential applications in preventing tumor progression in neuroblastoma-prone offspring. Full article
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Article
Adjuvantation of Pulmonary-Administered Influenza Vaccine with GPI-0100 Primarily Stimulates Antibody Production and Memory B Cell Proliferation
by Harshad P. Patil, José Herrera Rodriguez, Jacqueline De Vries-Idema, Tjarko Meijerhof, Henderik W. Frijlink, Wouter L. J. Hinrichs and Anke Huckriede
Vaccines 2017, 5(3), 19; https://doi.org/10.3390/vaccines5030019 - 27 Jul 2017
Cited by 4 | Viewed by 4911
Abstract
Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and [...] Read more.
Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and whole inactivated influenza virus (WIV) vaccine administered via the pulmonary route. However, the impact of the GPI-0100 dose on immune stimulation and the immune mechanisms stimulated by GPI-0100 along with antigen are poorly understood. Therefore, in this study we immunized C57BL/6 mice via the pulmonary route with vaccine consisting of WIV combined with increasing amounts of GPI-0100, formulated as a dry powder. Adjuvantation of WIV enhanced influenza-specific mucosal and systemic immune responses, with intermediate doses of 5 and 7.5 μg GPI-0100 being most effective. The predominant antibody subtype induced by GPI-0100-adjuvanted vaccine was IgG1. Compared to non-adjuvanted vaccine, GPI-0100-adjuvanted WIV vaccine gave rise to higher numbers of antigen-specific IgA- but not IgG-producing B cells in the lungs along with better mucosal and systemic memory B cell responses. The GPI-0100 dose was negatively correlated with the number of influenza-specific IFNγ- and IL17-producing T cells and positively correlated with the number of IL4-producing T cells observed after immunization and challenge. Overall, our results show that adjuvantation of pulmonary-delivered WIV with GPI-0100 mostly affects B cell responses and effectively induces B cell memory. Full article
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Review
Egg-Independent Influenza Vaccines and Vaccine Candidates
by Ilaria Manini, Claudia Maria Trombetta, Giacomo Lazzeri, Teresa Pozzi, Stefania Rossi and Emanuele Montomoli
Vaccines 2017, 5(3), 18; https://doi.org/10.3390/vaccines5030018 - 18 Jul 2017
Cited by 48 | Viewed by 11795
Abstract
Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a [...] Read more.
Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines. Full article
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Article
Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population
by Ivan Sanz, Silvia Rojo, Sonia Tamames, José María Eiros and Raúl Ortiz de Lejarazu
Vaccines 2017, 5(3), 17; https://doi.org/10.3390/vaccines5030017 - 17 Jul 2017
Cited by 7 | Viewed by 3878
Abstract
Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and [...] Read more.
Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad response of heterotypic antibodies against avian influenza viruses, albeit at a low level. Full article
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Article
The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection
by Abhijeet A. Bakre, Jennifer L. Harcourt, Lia M. Haynes, Larry J. Anderson and Ralph A. Tripp
Vaccines 2017, 5(3), 16; https://doi.org/10.3390/vaccines5030016 - 03 Jul 2017
Cited by 23 | Viewed by 5473
Abstract
Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. [...] Read more.
Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting. Full article
(This article belongs to the Special Issue Host Responses to Viral Infection)
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