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Vaccines, Volume 8, Issue 3 (September 2020) – 109 articles

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Open AccessArticle
Vaccine Efficacy on the Novel Reassortant H9N2 Virus in Indonesia
Vaccines 2020, 8(3), 449; https://doi.org/10.3390/vaccines8030449 (registering DOI) - 10 Aug 2020
Viewed by 170
Abstract
Vaccination is one of the leading methods of controlling the spread of the Avian Influenza (AI) viruses in Indonesia. The variety of circulating viruses and their ability to mutate must be followed by updating the vaccine master seed used in the field. In [...] Read more.
Vaccination is one of the leading methods of controlling the spread of the Avian Influenza (AI) viruses in Indonesia. The variety of circulating viruses and their ability to mutate must be followed by updating the vaccine master seed used in the field. In this study, we identified the reassortant H9N2 viruses in chicken farms that showed significant problems in decreased egg production with high mortality. The reassortant H9N2 viruses derived the PB2 gene from the H5N1 virus. The pathogenicity test results of the reassortant virus showed various clinical signs of illness, a high mortality rate (10%), and decreased egg production down to 63.12% at two weeks post-infection. In a vaccine efficacy test, the vaccinated groups showed minimally decreased egg production that started to increase to more than 80% at 4–7 weeks post-challenge. Our study showed that inactivated bivalent and monovalent reassortant H9N2 vaccines can induce antibody response, reducing the mortality and virus shedding caused by reassortant H9N2 virus infection. The reassortant H9N2 virus is a threat that requires vigilance in poultry farms and the industry. The vaccines used in this study can be one of the options for control or prevention measures on farms infected with the reassortant H9N2 viruses. Full article
(This article belongs to the Special Issue Poultry Vaccines)
Open AccessArticle
Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice
Vaccines 2020, 8(3), 448; https://doi.org/10.3390/vaccines8030448 - 09 Aug 2020
Viewed by 222
Abstract
Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated [...] Read more.
Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated response, since they contain conservative epitopes capable to induce antibodies and cytotoxic T lymphocytes (CTLs) to a wide range of influenza virus subtypes. Methods: In this study, we generated DNA vaccine constructs encoding artificial antigens AgH1, AgH3, and AgM2 designed on the basis of conservative hemagglutinin stem fragments of two influenza A virus subtypes, H1N1 and H3N2, and conservative M2 protein, and evaluate their immunogenicity and protective efficacy. To obtain DNA vaccine constructs, genes encoding the designed antigens were cloned into a pcDNA3.1 vector. Expression of the target genes in 293T cells transfected with DNA vaccine constructs has been confirmed by synthesis of specific mRNA. Results: Immunization of BALB/c mice with DNA vaccines encoding these antigens was shown to evoke humoral and T-cell immune responses as well as a moderated statistically significant cross-protective effect against two heterologous viruses A/California/4/2009 (H1N1pdm09) and A/Aichi/2/68 (H3N2). Conclusions: The results demonstrate a potential approach to creating a universal influenza vaccine based on artificial antigens. Full article
(This article belongs to the Special Issue Influenza Virus and Vaccine Development)
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Open AccessReview
Immuno-Oncotherapeutic Approaches in Advanced Hepatocellular Carcinoma
Vaccines 2020, 8(3), 447; https://doi.org/10.3390/vaccines8030447 - 08 Aug 2020
Viewed by 172
Abstract
Advanced hepatocellular carcinoma has limited treatment options, but there has been extensive growth recently with cabozantinib, regorafenib, lenvatinib, nivolumab, atezolizumab, and bevacizumab, which are some of the treatments that have received FDA approval just over the last three years. Because HCC tumor microenvironment [...] Read more.
Advanced hepatocellular carcinoma has limited treatment options, but there has been extensive growth recently with cabozantinib, regorafenib, lenvatinib, nivolumab, atezolizumab, and bevacizumab, which are some of the treatments that have received FDA approval just over the last three years. Because HCC tumor microenvironment is potentially immunogenic and typically characterized by inflammation, immunotherapy has been proposed as a potential novel therapeutic approach, which has prompted studies in advanced HCC patients investigating various immune-therapeutic strategies such as CAR-T cell therapy, checkpoint inhibitors, and onco-vaccines. The anti-PD-1 checkpoint inhibitors nivolumab and pembrolizumab have been FDA approved as a second line treatment in patients who progressed or are intolerant to Sorafenib. To build up on the success of PD-1 monotherapy, combinatorial regimens with PD-1/PD-L1 inhibitors plus VEGF targeted agents have shown positive results in various malignancies including HCC. The combination of atezolizumab plus bevacizumab is the new addition to the HCC treatment armamentarium following a pivotal study that demonstrated an improvement in OS over frontline sorafenib. Other novel immune-based approaches and oncolytic viruses are in the early phases of clinical evaluation. These innovative approaches enhance the intensity of cancer-directed immune responses and will potentially impact the outlook of this aggressive disease. Full article
(This article belongs to the Special Issue Cancer Vaccine)
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Open AccessArticle
Evaluating the Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine Compared to High-Dose Trivalent and Other Egg-Based Influenza Vaccines among Older Adults in the US during the 2017–2018 Influenza Season
Vaccines 2020, 8(3), 446; https://doi.org/10.3390/vaccines8030446 - 07 Aug 2020
Viewed by 193
Abstract
The influenza-related disease burden is highest among the elderly. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to other egg-based influenza vaccines (high-dose trivalent (TIV-HD), quadrivalent (QIVe-SD), and standard-dose trivalent (TIVe-SD)) against influenza-related and cardio-respiratory events among [...] Read more.
The influenza-related disease burden is highest among the elderly. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to other egg-based influenza vaccines (high-dose trivalent (TIV-HD), quadrivalent (QIVe-SD), and standard-dose trivalent (TIVe-SD)) against influenza-related and cardio-respiratory events among subjects aged ≥65 years for the 2017–2018 influenza season. This retrospective cohort analysis used prescription claims, professional fee claims, and hospital charge master data. Influenza-related hospitalizations/ER visits and office visits and cardio-respiratory events were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of aTIV compared to other vaccines. In an economic analysis, annualized follow-up costs were compared between aTIV and TIV-HD. The study was composed of 234,313 aTIV, 1,269,855 TIV-HD, 212,287 QIVe-SD, and 106,491 TIVe-SD recipients. aTIV was more effective in reducing influenza-related office visits and other respiratory-related hospitalizations/ER visits compared to the other vaccines. For influenza-related hospitalizations/ER visits, aTIV was associated with a significantly higher rVE compared to QIVe-SD and TIVe-SD and was comparable to TIV-HD. aTIV was also associated with a significantly higher rVE compared to TIVe-SD against hospitalizations/ER visits related to pneumonia and asthma/COPD/bronchial events. aTIV and TIV-HD were associated with comparable annualized all-cause and influenza-related costs. Adjusted analyses demonstrated a significant benefit of aTIV against influenza- and respiratory-related events compared to the other egg-based vaccines. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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Open AccessEditorial
Invited Editorial: Despite COVID-19, Influenza Must Not Be Relegated to “Only the Sniffles”
Vaccines 2020, 8(3), 445; https://doi.org/10.3390/vaccines8030445 - 07 Aug 2020
Viewed by 227
Abstract
As the current COVID-19 pandemic continues to rage worldwide, it has emerged that the 2019–2020 influenza season has been milder and shorter than usual in the northern hemisphere, presumably due to enforced social distancing [...] Full article
Open AccessArticle
SARS-CoV-2 Consensus-Sequence and Matching Overlapping Peptides Design for COVID19 Immune Studies and Vaccine Development
Vaccines 2020, 8(3), 444; https://doi.org/10.3390/vaccines8030444 - 06 Aug 2020
Viewed by 211
Abstract
Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to [...] Read more.
Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to test immune responses in exposed and infected individuals at the population level. To accelerate immune studies in SARS-CoV-2 infection, we here describe a SARS-CoV-2 2020 consensus sequence (CoV-2-cons) which is based on more than 1700 viral genome entries in NCBI and encompasses all described SARS-CoV-2 open reading frames (ORF), including recently described frame-shifted and length variant ORF. Based on these sequences, we created curated overlapping peptide (OLP) lists containing between 1500 to 3000 peptides of 15 and 18 amino acids in length, overlapping by 10 or 11 residues, as ideal tools for the assessment of SARS-CoV-2-specific T cell immunity. In addition, CoV-2-cons sequence entropy values are presented along with variant sequences to provide increased coverage of the most variable sections of the viral genome. The identification of conserved protein fragments across the coronavirus family and the corresponding OLP facilitate the identification of T cells potentially cross-reactive with related viruses. This new CoV-2-cons sequence, together with the peptides sets, should provide the basis for SARS-CoV-2 antigen synthesis to facilitate comparability between ex-vivo immune analyses and help to accelerate research on SARS-CoV-2 immunity and vaccine development. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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Open AccessReview
Investigating Virological, Immunological, and Pathological Avenues to Identify Potential Targets for Developing COVID-19 Treatment and Prevention Strategies
Vaccines 2020, 8(3), 443; https://doi.org/10.3390/vaccines8030443 - 06 Aug 2020
Viewed by 296
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs considerably from individual to individual. Investigating the virology of COVID-19 and immunological pathways underlying its clinical manifestations will enable the identification and design of effective vaccines and potential therapies. In this review, we explore COVID-19 virology, the contribution of the immune system (innate and adaptive) during infection and control of the virus. Finally, we highlight vaccine development and implications of immune system modulation for potential therapeutic interventions to design better therapeutic strategies to guide future cure. Full article
(This article belongs to the Special Issue B and T Cell-Mediated Immunity)
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Open AccessReview
Antiretroviral Therapy Interruption (ATI) in HIV-1 Infected Patients Participating in Therapeutic Vaccine Trials: Surrogate Markers of Virological Response
Vaccines 2020, 8(3), 442; https://doi.org/10.3390/vaccines8030442 - 05 Aug 2020
Viewed by 312
Abstract
A functional Human immunodeficiency Virus (HIV) cure has been proposed as an alternative to antiretroviral treatment for life, and therapeutic vaccines represent one of the most promising approaches. The goal of therapeutic vaccination is to augment virus-specific immune responses that have an impact [...] Read more.
A functional Human immunodeficiency Virus (HIV) cure has been proposed as an alternative to antiretroviral treatment for life, and therapeutic vaccines represent one of the most promising approaches. The goal of therapeutic vaccination is to augment virus-specific immune responses that have an impact on HIV viral load dynamics. To date, the agreed feature to evaluate the effects of these therapeutic interventions is analytical antiretroviral treatment interruption (ATI), at least until we find a reliable biomarker that can predict viral control. Different host, immunologic, and virologic markers have been proposed as predictors of viral control during ATI after therapeutic interventions. This review describes the relevance of ATI and the different surrogate markers of virological control assessed in HIV therapeutic vaccine clinical trials. Full article
(This article belongs to the Special Issue Therapeutic Vaccination of HIV-infected Patients)
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Open AccessArticle
Novel Trivalent Vectored Vaccine for Control of Myxomatosis and Disease Caused by Classical and a New Genotype of Rabbit Haemorrhagic Disease Virus
Vaccines 2020, 8(3), 441; https://doi.org/10.3390/vaccines8030441 - 05 Aug 2020
Viewed by 201
Abstract
Myxoma virus (MV) and rabbit haemorrhagic disease virus (RHDV) are the major causes of lethal viral diseases in the European rabbit. In 2010, a new RHDV genotype (RHDV2) emerged in the field that had limited cross-protection with the classical RHDV (RHDV1). For optimal [...] Read more.
Myxoma virus (MV) and rabbit haemorrhagic disease virus (RHDV) are the major causes of lethal viral diseases in the European rabbit. In 2010, a new RHDV genotype (RHDV2) emerged in the field that had limited cross-protection with the classical RHDV (RHDV1). For optimal protection of rabbits and preventing spread of disease, a vaccine providing protection against all three key viruses would be ideal. Therefore, a novel trivalent myxoma vectored RHDV vaccine (Nobivac Myxo-RHD PLUS) was developed similar to the existing bivalent myxoma vectored RHDV vaccine Nobivac Myxo-RHD. The new vaccine contains the Myxo-RHDV1 strain already included in Nobivac Myxo-RHD and a similarly produced Myxo-RHDV2 strain. This paper describes several key safety and efficacy studies conducted for European licensing purposes. Nobivac Myxo-RHD PLUS showed to be safe for use in rabbits from five weeks of age onwards, including pregnant rabbits, and did not spread from vaccinated rabbits to in-contact controls. Furthermore, protection to RHDV1 and RHDV2 was demonstrated by challenge, while the serological response to MV was similar to that after vaccination with Nobivac Myxo-RHD. Therefore, routine vaccination with Nobivac Myxo-RHD PLUS can prevent the kept rabbit population from these major viral diseases. Full article
Open AccessArticle
Optimized Hepatitis C Virus (HCV) E2 Glycoproteins and their Immunogenicity in Combination with MVA-HCV
Vaccines 2020, 8(3), 440; https://doi.org/10.3390/vaccines8030440 - 05 Aug 2020
Viewed by 281
Abstract
Hepatitis C virus (HCV) represents a major global health challenge and an efficient vaccine is urgently needed. Many HCV vaccination strategies employ recombinant versions of the viral E2 glycoprotein. However, recombinant E2 readily forms disulfide-bonded aggregates that might not be optimally suited for [...] Read more.
Hepatitis C virus (HCV) represents a major global health challenge and an efficient vaccine is urgently needed. Many HCV vaccination strategies employ recombinant versions of the viral E2 glycoprotein. However, recombinant E2 readily forms disulfide-bonded aggregates that might not be optimally suited for vaccines. Therefore, we have designed an E2 protein in which we strategically changed eight cysteines to alanines (E2.C8A). E2.C8A formed predominantly monomers and virtually no aggregates. Furthermore, E2.C8A also interacted more efficiently with broadly neutralizing antibodies than conventional E2. We used mice to evaluate different prime/boost immunization strategies involving a modified vaccinia virus Ankara (MVA) expressing the nearly full-length genome of HCV (MVA-HCV) in combination with either the E2 aggregates or the E2.C8A monomers. The combined MVA-HCV/E2 aggregates prime/boost strategy markedly enhanced HCV-specific effector memory CD4+ T cell responses and antibody levels compared to MVA-HCV/MVA-HCV. Moreover, the aggregated form of E2 induced higher levels of anti-E2 antibodies in vaccinated mice than E2.C8A monomers. These antibodies were cross-reactive and mainly of the IgG1 isotype. Our findings revealed how two E2 viral proteins that differ in their capacity to form aggregates are able to enhance to different extent the HCV-specific cellular and humoral immune responses, either alone or in combination with MVA-HCV. These combined protocols of MVA-HCV/E2 could serve as a basis for the development of a more effective HCV vaccine. Full article
(This article belongs to the Section Hepatitis Virus Vaccines)
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Open AccessEditorial
Listeria monocytogenes as a Vector for Cancer Immunotherapy
Vaccines 2020, 8(3), 439; https://doi.org/10.3390/vaccines8030439 - 05 Aug 2020
Viewed by 216
Abstract
Cancer is a wide group of diseases, which was responsible for 9.6 million deaths in 2018. Cancer immunotherapies have become a reality, with the first approval for sipuleucel-T for prostate cancer therapy occurring in 2010. Listeria monocytogenes is a Gram-positive bacterium, mostly known [...] Read more.
Cancer is a wide group of diseases, which was responsible for 9.6 million deaths in 2018. Cancer immunotherapies have become a reality, with the first approval for sipuleucel-T for prostate cancer therapy occurring in 2010. Listeria monocytogenes is a Gram-positive bacterium, mostly known as a food-borne pathogen, capable of causing life-threatening and often fatal infections. However, since in the majority of cases the human immune system is able to mount potent innate and adaptive immune responses that control infections by Listeria monocytogenes, the microorganism has become an attractive vector for the development of cancer vaccines. The review by Flickinger Jr., Rodeck and Snook (Vaccines 2018, 6, 48) on the use of Listeria monocytogenes as a vector for cancer immunotherapy is described and commented here. Full article
Open AccessArticle
Distinct miRNA Profile of Cellular and Extracellular Vesicles Released from Chicken Tracheal Cells Following Avian Influenza Virus Infection
Vaccines 2020, 8(3), 438; https://doi.org/10.3390/vaccines8030438 - 05 Aug 2020
Viewed by 352
Abstract
Innate responses provide the first line of defense against viral infections, including the influenza virus at mucosal surfaces. Communication and interaction between different host cells at the early stage of viral infections determine the quality and magnitude of immune responses against the invading [...] Read more.
Innate responses provide the first line of defense against viral infections, including the influenza virus at mucosal surfaces. Communication and interaction between different host cells at the early stage of viral infections determine the quality and magnitude of immune responses against the invading virus. The release of membrane-encapsulated extracellular vesicles (EVs), from host cells, is defined as a refined system of cell-to-cell communication. EVs contain a diverse array of biomolecules, including microRNAs (miRNAs). We hypothesized that the activation of the tracheal cells with different stimuli impacts the cellular and EV miRNA profiles. Chicken tracheal rings were stimulated with polyI:C and LPS from Escherichia coli 026:B6 or infected with low pathogenic avian influenza virus H4N6. Subsequently, miRNAs were isolated from chicken tracheal cells or from EVs released from chicken tracheal cells. Differentially expressed (DE) miRNAs were identified in treated groups when compared to the control group. Our results demonstrated that there were 67 up-regulated miRNAs, 157 down-regulated miRNAs across all cellular and EV samples. In the next step, several genes or pathways targeted by DE miRNAs were predicted. Overall, this study presented a global miRNA expression profile in chicken tracheas in response to avian influenza viruses (AIV) and toll-like receptor (TLR) ligands. The results presented predicted the possible roles of some DE miRNAs in the induction of antiviral responses. The DE candidate miRNAs, including miR-146a, miR-146b, miR-205a, miR-205b and miR-449, can be investigated further for functional validation studies and to be used as novel prophylactic and therapeutic targets in tailoring or enhancing antiviral responses against AIV. Full article
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Open AccessArticle
Vaccination of Mice with a Novel Trypsin from Trichinella spiralis Elicits the Immune Protection against Larval Challenge
Vaccines 2020, 8(3), 437; https://doi.org/10.3390/vaccines8030437 - 05 Aug 2020
Viewed by 227
Abstract
Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel [...] Read more.
Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel T. spiralis trypsin (TsT) and its elicited immune protection against larval challenge. The cDNA sequence of TsT gene was cloned and expressed. Western blotting showed rTsT was identified by infection serum and anti-TsT serum. RT-PCR results revealed that TsT gene was transcribed at diverse T. spiralis lifecycle stages. The IIFT results showed that natural TsT was principally expressed at epicuticle of 5-6 day adult worms, indicating that TsT is a worm somatic antigen and adult-stage specific surface antigen. Vaccination of mice with rTsT triggered an evident humoral immune response (high levels of serum IgG, IgG1/IgG2a, and enteral sIgA), and it also induced the systemic and enteral local cellular immune response, demonstrated by an significantly elevation of cytokines IFN-γ and IL-4. The mice vaccinated with rTsT exhibited a 33.17% reduction of enteral adult worms and a 37.80% reduction of muscle larvae after larval challenge. The results showed that TsT might be considered as a candidate target antigen for anti-T. spiralis vaccines. Full article
(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)
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Open AccessPerspective
Natural Self-Ligand Gamma Delta T Cell Receptors (γδTCRs) Insight: The Potential of Induced IgG
Vaccines 2020, 8(3), 436; https://doi.org/10.3390/vaccines8030436 - 04 Aug 2020
Viewed by 288
Abstract
A γδ T cell acquires functional properties in response to the gamma delta T cell receptor γδTCR signal strength during its development in the thymus. The elucidation of the potential ligands of γδ T cell receptors are of extreme importance; however, they are [...] Read more.
A γδ T cell acquires functional properties in response to the gamma delta T cell receptor γδTCR signal strength during its development in the thymus. The elucidation of the potential ligands of γδ T cell receptors are of extreme importance; however, they are still not understood. Here we revise the actual state of the art of candidates to exert the function of γδTCR ligands, and propose a theoretical contribution about new potential ligands of γδTCRs, based on biological and hypothetical pieces of evidence in the literature. In conclusion, we hypothetically suggest a possible role of induced antibodies according to the individual’s immune status, mainly of the IgG subclass, acting as γδTCR ligands. Considering that IgG production is involved in some essential immunotherapy protocols, and almost all vaccination protocols, our discussion opens a new and broad field to further exploration. Full article
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Open AccessArticle
Maximization of Livestock Anthrax Vaccination Coverage in Bangladesh: An Alternative Approach
Vaccines 2020, 8(3), 435; https://doi.org/10.3390/vaccines8030435 - 04 Aug 2020
Viewed by 434
Abstract
Low vaccination coverage of livestock is one of the major challenges to control anthrax in Bangladesh. This study was conducted to assess an alternate approach to maximize vaccination coverage. The method included traditional vaccination campaigns, livestock census, interviews, focus group discussions of cattle [...] Read more.
Low vaccination coverage of livestock is one of the major challenges to control anthrax in Bangladesh. This study was conducted to assess an alternate approach to maximize vaccination coverage. The method included traditional vaccination campaigns, livestock census, interviews, focus group discussions of cattle farmers, vaccination and livestock personnel, and validation workshops. It was observed that a mass vaccination program covered only 44% of the cattle population. It was found that 54.1% of the respondents did not bring their cattle to mass vaccination programs due to the difficulties of handling cattle and that there was no male member in the household. Only 12.5% of respondents acknowledged that they were not aware of the vaccine, and 3% of the respondents claimed that they ignored vaccination due to cost. All of the respondents from livestock personnel agreed that manpower was not enough to cover the total area. Further, 20% of vaccinators mentioned that they did not get enough vaccines. For an effective vaccination program, 58.33% of respondents recommended door-to-door service, and 54.16% of respondents suggested to arrange regular vaccination campaigns in six-month intervals. Thus, regular campaigns with door-to-door vaccination services are suggested to control anthrax outbreaks in Bangladesh. Full article
(This article belongs to the Section Veterinary Vaccines)
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Open AccessReview
Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine
Vaccines 2020, 8(3), 434; https://doi.org/10.3390/vaccines8030434 - 03 Aug 2020
Viewed by 416
Abstract
Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, [...] Read more.
Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection. Full article
(This article belongs to the Special Issue Development of Cross-Protective Vaccines)
Open AccessArticle
Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses
Vaccines 2020, 8(3), 433; https://doi.org/10.3390/vaccines8030433 - 03 Aug 2020
Viewed by 275
Abstract
Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared [...] Read more.
Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety. Full article
(This article belongs to the Special Issue Vaccinology of Influenza Infection)
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Open AccessEditorial
The Adoption of Viral Capsid-Derived Virus-Like Particles (VLPs) for Disease Prevention and Treatments
Vaccines 2020, 8(3), 432; https://doi.org/10.3390/vaccines8030432 - 02 Aug 2020
Viewed by 318
Abstract
In the present paper, Mohosen et al [...] Full article
Open AccessArticle
Incidence of Guillain-Barré Syndrome Is Not Associated with Influenza Vaccination in the Elderly
Vaccines 2020, 8(3), 431; https://doi.org/10.3390/vaccines8030431 (registering DOI) - 31 Jul 2020
Viewed by 325
Abstract
We aimed to analyze the incidence of Guillain-Barré syndrome (GBS) and its association with influenza vaccination (IV) in the elderly population. This study included 2470 patients hospitalized with GBS (G61.0) between 2014 and 2016 based on the Korean National Health Insurance Service (NHIS) [...] Read more.
We aimed to analyze the incidence of Guillain-Barré syndrome (GBS) and its association with influenza vaccination (IV) in the elderly population. This study included 2470 patients hospitalized with GBS (G61.0) between 2014 and 2016 based on the Korean National Health Insurance Service (NHIS) claims data. We reviewed every medical claim in the 42 days preceding GBS diagnosis looking for precedent causes of GBS. To assess the relationship between IV and the development of GBS, data from the NHIS and the National Vaccination Registry were combined and analyzed. Using a self-controlled case series (SCCS) approach, we calculated the incidence rate ratio by setting the risk period as 42 days following vaccination. The annual background incidence of GBS was estimated at 4.15 per 100,000 persons. More than half of the patients with newly developed GBS had a previous infection or surgery. The incidence of GBS within 42 days of IV was estimated at 0.32 per 100,000 vaccinated persons. SCCS analysis showed that the risk of GBS was not significantly higher. While GBS can potentially develop from various infections, no association was found between GBS and IV. These results will contribute to developing an evidence-based vaccine policy that includes a clear causality assessment of adverse events. Full article
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Open AccessEditorial
Nanometric Virus-Like Particles: Key Tools for Vaccine and Adjuvant Technology
Vaccines 2020, 8(3), 430; https://doi.org/10.3390/vaccines8030430 - 31 Jul 2020
Viewed by 281
Abstract
The ideal vaccine should trigger a specific response against pathogens and induce the immune system memory to be prepared for eventual following infections. Although different approaches to develop new vaccines are currently taken, several of the features of natural pathogens that allow a [...] Read more.
The ideal vaccine should trigger a specific response against pathogens and induce the immune system memory to be prepared for eventual following infections. Although different approaches to develop new vaccines are currently taken, several of the features of natural pathogens that allow a tailored immune reaction are difficult to mimic. The viral capsids are the physical interface between a virus and the host defense machinery which recognizes specific patterns of the viral supramolecular complexes. Therefore, empty viral particles deprived of their genomes represent optimal targets to induce immune reactions with several advantages for vaccination and adjuvant realization. Full article
Open AccessArticle
The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines
Vaccines 2020, 8(3), 429; https://doi.org/10.3390/vaccines8030429 - 30 Jul 2020
Viewed by 379
Abstract
The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain [...] Read more.
The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain insight into which antigens contribute to protection. We showed that total depletion of virulence factors (bvg(-) mode) in omvPV led to diminished protection despite the presence of high antibody levels. Antibody profiling revealed overlap in humoral responses induced by vaccines in bvg(-) and bvg(+) mode, but the potentially protective responses in the bvg(+) vaccine were mainly directed against virulence-associated outer membrane proteins (virOMPs) such as BrkA and Vag8. However, deletion of either BrkA or Vag8 in our outer membrane vesicle vaccines did not affect the level of protection. In addition, the vaccine-induced immunity profile, which encompasses broad antibody and mixed T-helper 1, 2 and 17 responses, was not changed. We conclude that the presence of multiple virOMPs in omvPV is crucial for protection against Bordetella pertussis. This protective immunity does not depend on individual proteins, as their absence or low abundance can be compensated for by other virOMPs. Full article
(This article belongs to the Special Issue Next-Generation Pertussis Vaccines)
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Open AccessArticle
Protective Immunity Induced by Virus-Like Particle Containing Merozoite Surface Protein 9 of Plasmodium berghei
Vaccines 2020, 8(3), 428; https://doi.org/10.3390/vaccines8030428 - 30 Jul 2020
Viewed by 327
Abstract
Merozoite surface protein 9 (MSP-9) from Plasmodium has shown promise as a vaccine candidate due to its location and possible role in erythrocyte invasion. In this study, we generated virus-like particles (VLPs) targeting P. berghei MSP-9, and investigated the protection against lethal doses [...] Read more.
Merozoite surface protein 9 (MSP-9) from Plasmodium has shown promise as a vaccine candidate due to its location and possible role in erythrocyte invasion. In this study, we generated virus-like particles (VLPs) targeting P. berghei MSP-9, and investigated the protection against lethal doses of P. berghei in a mouse model. We found that VLP vaccination induced a P. berghei-specific IgG antibody response in the sera and CD4+ and CD8+ T cell populations in blood compared to a naïve control group. Upon challenge infection with P. berghei, vaccinated mice showed a significant increase in CD4+ and CD8+ effector memory T cell and memory B cell populations. Importantly, MSP-9 VLP immunization inhibited levels of the pro-inflammatory cytokines IFN-γ and IL-6 in the spleen and parasite replication in blood, resulting in significantly prolonged survival time. These results suggest that the MSP-9 VLP vaccine may constitute an effective malaria vaccine. Full article
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Open AccessArticle
Moderate Vaccine Effectiveness against Severe Acute Respiratory Infection Caused by A(H1N1)pdm09 Influenza Virus and No Effectiveness against A(H3N2) Influenza Virus in the 2018/2019 Season in Italy
Vaccines 2020, 8(3), 427; https://doi.org/10.3390/vaccines8030427 - 30 Jul 2020
Viewed by 357
Abstract
Every season, circulating influenza viruses change; therefore, vaccines must be reformulated each year. We aimed to estimate vaccine effectiveness (VE) against severe influenza infection for the 2018/19 season in Italy. We conducted a test-negative design case-control study at five Italian hospitals. We estimated [...] Read more.
Every season, circulating influenza viruses change; therefore, vaccines must be reformulated each year. We aimed to estimate vaccine effectiveness (VE) against severe influenza infection for the 2018/19 season in Italy. We conducted a test-negative design case-control study at five Italian hospitals. We estimated influenza VE against severe acute respiratory infection (SARI) requiring hospitalisation overall, and by virus subtype, vaccine brand, and age. The 2018/19 season was characterised by A(H1N1)pmd09 and A(H3N2) influenza viruses. Vaccine coverage among <18 years recruited SARI cases was very low (3.2%). Seasonal vaccines were moderately effective against type A influenza overall (adjusted VE = 40.5%; 95% confidence interval (CI) = 18.7–56.4%) and subtype A(H1N1)pmd09 viruses (adjusted VE = 55%; 95% CI = 34.5–69.1%), but ineffective against subtype A(H3N2) viruses (adjusted VE = 2.5%; 95% CI = −50.0–36.7%). Both Fluad and Fluarix Tetra vaccines were effective against type A influenza overall and subtype A(H1N1)pdm09 viruses. VE appeared to be similar across age groups (0–64 years, ≥65 years). Seasonal influenza vaccines in the 2018/19 season were moderately effective in preventing SARI caused by A(H1N1)pdm09 influenza but ineffective against A(H3N2). Full article
(This article belongs to the Section Influenza Virus Vaccines)
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Open AccessReview
Pneumococcal Vaccination for Children in Asian Countries: A Systematic Review of Economic Evaluation Studies
Vaccines 2020, 8(3), 426; https://doi.org/10.3390/vaccines8030426 - 30 Jul 2020
Viewed by 302
Abstract
Background: Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness [...] Read more.
Background: Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness of implementing and adopting a PCV vaccination program. Methods: We conducted a systematic review from Pubmed and Embase to identify economic evaluation studies of PCV for children in Asian countries up to May 2020. Data extraction included specific characteristics of the study, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement was followed for this systematic review. The reporting quality of the included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Results: After the screening process on both the title and abstract and full text of 518 records, a total of 25 studies fulfilled the inclusion criteria, and were included in the review. The majority of included studies demonstrates that PCV for children is cost-effective in most of the Asian region, and even cost-saving in some countries. Most of the included studies implemented cost utility analysis (CUA) using either quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Overall, the main drivers affecting the cost effectiveness were vaccine price, burden regarding pneumonia-related parameters, and the inclusion of herd effects. Conclusion: The children pneumococcal vaccination program appears to be a cost-effective intervention in Asia, and even cost-saving in certain conditions. Vaccine price, pneumonia-related disease burden, and the inclusion of the herd effect are observed as important key drivers in estimating cost-effectiveness in this region. Incorporating PCV in vaccination programs in this region was found to be highly favorable. Full article
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Open AccessArticle
Epidemiologic Profile of Type-Specific Human Papillomavirus Infection after Initiation of HPV Vaccination
Vaccines 2020, 8(3), 425; https://doi.org/10.3390/vaccines8030425 - 29 Jul 2020
Viewed by 227
Abstract
Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12–16 years who were born in 1994 or later. The rate of OHPV coverage was 70–80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We [...] Read more.
Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12–16 years who were born in 1994 or later. The rate of OHPV coverage was 70–80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We aim to investigate the change in prevalence of HPV infection after the initiation of HPV vaccination. We recruited females aged 20–21 years attending public cervical cancer screening from 2014 to 2017 fiscal years (April 2014 to March 2018). Residual Pap test specimens were collected for HPV testing. We compared the prevalence of HPV type-specific infection between women registered in 2014 (born in 1993–1994, including the pre-OHPV generation) and registered in 2015–2017 (born in 1994–1997, the OHPV generation). We collected 2379 specimens. The vaccination coverage figures were 30.7%, 86.6%, 88.4% and 93.7% (p < 0.01) from 2014 to 2017, respectively. The prevalence of HPV16/18 infection significantly decreased from 1.3% in 2014 to 0% in 2017 (p = 0.02). The three most prevalent types were HPV52, 16 and 56 in 2014, and HPV52, 58 and 56 in 2015–2017, respectively. HPV16 and 33 infection rates decreased. On the other hand, the HPV58 infection rate was obviously increased after OHPV from 0.3% to 2.1%. Our study demonstrates that the prevalence of HPV16/18 infection dramatically decreased and the profile of type-specific HPV infection was changed after OHPV. Full article
(This article belongs to the Special Issue Development of Cross-Protective Vaccines)
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Open AccessReview
Broadly Neutralizing Antibodies for Influenza: Passive Immunotherapy and Intranasal Vaccination
Vaccines 2020, 8(3), 424; https://doi.org/10.3390/vaccines8030424 - 29 Jul 2020
Viewed by 244
Abstract
Influenza viruses cause annual epidemics and occasional pandemics. The high diversity of viral envelope proteins permits viruses to escape host immunity. Therefore, the development of a universal vaccine and broadly neutralizing antibodies (bnAbs) is essential for controlling various mutant viruses. Here, we review [...] Read more.
Influenza viruses cause annual epidemics and occasional pandemics. The high diversity of viral envelope proteins permits viruses to escape host immunity. Therefore, the development of a universal vaccine and broadly neutralizing antibodies (bnAbs) is essential for controlling various mutant viruses. Here, we review some potentially valuable bnAbs for influenza; one is a novel passive immunotherapy using a variable domain of heavy chain-only antibody (VHH), and the other is polymeric immunoglobulin A (pIgA) induced by intranasal vaccination. Recently, it was reported that a tetravalent multidomain antibody (MDAb) was developed by genetic fusion of four VHHs, which are bnAbs against the influenza A or B viruses. The transfer of a gene encoding the MDAb–Fc fusion protein provided cross-protection against both influenza A and B viruses in vivo. An intranasal universal influenza vaccine, which can induce neutralizing pIgAs in the upper respiratory tract, is currently undergoing clinical studies. A recent study has revealed that tetrameric IgAs formed in nasal mucosa are more broadly protective against influenza than the monomeric and dimeric forms. These broadly neutralizing antibodies have high potential to control the currently circulating influenza virus. Full article
(This article belongs to the Special Issue Development of Cross-Protective Vaccines)
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Open AccessArticle
Vaccine Design from the Ensemble of Surface Glycoprotein Epitopes of SARS-CoV-2: An Immunoinformatics Approach
Vaccines 2020, 8(3), 423; https://doi.org/10.3390/vaccines8030423 - 28 Jul 2020
Viewed by 463
Abstract
The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL [...] Read more.
The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. From the overlapped epitopes, we designed five vaccine constructs C1–C5. Based on antigenicity, allergenicity, solubility, different physiochemical properties, and molecular docking scores, we selected the vaccine construct 1 (C1) for further processing. Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of −43.48, −65.88, and −60.24 Kcal/mol, respectively. The docked complex was further simulated, which revealed that both molecules remain stable with minimum RMSF. Activation of TLRs induces downstream pathways to produce pro-inflammatory cytokines against viruses and immune system simulation shows enhanced antibody production after the booster dose. In conclusion, C1 was the best vaccine candidate among all designed constructs to elicit an immune response SARS-CoV-2 and combat the coronavirus disease (COVID-19). Full article
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Open AccessReview
Hepatitis E Virus: How It Escapes Host Innate Immunity
Vaccines 2020, 8(3), 422; https://doi.org/10.3390/vaccines8030422 - 28 Jul 2020
Viewed by 259
Abstract
Hepatitis E virus (HEV) is a leading cause of viral hepatitis in the world. It is usually responsible for acute hepatitis, but can lead to a chronic infection in immunocompromised patients. The host’s innate immune response is the first line of defense against [...] Read more.
Hepatitis E virus (HEV) is a leading cause of viral hepatitis in the world. It is usually responsible for acute hepatitis, but can lead to a chronic infection in immunocompromised patients. The host’s innate immune response is the first line of defense against a virus infection; there is growing evidence that HEV RNA is recognized by toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), leading to interferon (IFN) production. The IFNs activate interferon-stimulated genes (ISGs) to limit HEV replication and spread. HEV has developed strategies to counteract this antiviral response, by limiting IFN induction and signaling. This review summarizes the advances in our knowledge of intracellular pathogen recognition, interferon and inflammatory response, and the role of virus protein in immune evasion. Full article
(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)
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Open AccessEditorial
Editorial On “Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy”
Vaccines 2020, 8(3), 421; https://doi.org/10.3390/vaccines8030421 - 28 Jul 2020
Viewed by 232
Abstract
The term “Exosomes” defines small extracellular vesicles, ranging from 30 to 150 nm in diameter, secreted by most eukaryotic cells into surrounding body fluids including blood, saliva, urine, bile and breast milk [...] Full article
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Open AccessReview
Vaccines against Genital Herpes: Where Are We?
Vaccines 2020, 8(3), 420; https://doi.org/10.3390/vaccines8030420 - 27 Jul 2020
Viewed by 311
Abstract
Genital herpes is a venereal disease caused by herpes simplex virus (HSV). Although HSV symptoms can be reduced with antiviral drugs, there is no cure. Moreover, because HSV infected individuals are often unaware of their infection, it is highly likely that they will [...] Read more.
Genital herpes is a venereal disease caused by herpes simplex virus (HSV). Although HSV symptoms can be reduced with antiviral drugs, there is no cure. Moreover, because HSV infected individuals are often unaware of their infection, it is highly likely that they will transmit HSV to their sexual partner. Once infected, an individual has to live with HSV for their entire life, and HSV infection can lead to meningitis, encephalitis, and neonatal herpes as a result of vertical transmission. In addition, HSV infection increases the rates of human immunodeficiency virus (HIV) infection and transmission. Because of the high burden of genital herpes, HSV vaccines have been developed, but none have been very successful. In this review, we discuss the current status of genital herpes vaccine development. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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