scholarly journals High immune efficacy against different avian influenza H5N1 viruses by oral administration of a Saccharomyces cerevisiae-based vaccine in chickens

2020 ◽  
Author(s):  
Han Lei ◽  
Qianhong Cen ◽  
Tong Gao ◽  
Yi Ren ◽  
Xin Lu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Avian Influenza ◽  
Oral Administration ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Oral Vaccine ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Effective Vaccine ◽  
Live Virus

Abstract BackgroundA safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional injection administration with a S. cerevisiae-based vaccine (EBY100/pYD1-HA) was protective against homologous H5N1 virus in a mouse model. Due to the diameter of S. cerevisiae is around 10 μm which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring cross-protection in poultry. ResultsWe extended our work by evaluating the immunogenicity and cross-protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided complete cross-protection against different H5N1 viruses challenge. ConclusionsThese findings suggest EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the drawbacks of conventional injection route. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

scholarly journals High immune efficacy against different avian influenza H5N1 viruses due to oral administration of a Saccharomyces cerevisiae-based vaccine in chickens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Han Lei ◽  
Xin Lu ◽  
Shuangqin Li ◽  
Yi Ren
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Avian Influenza ◽  
Oral Administration ◽  
Large Scale ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Oral Vaccine ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Live Virus

AbstractA safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 μm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

scholarly journals Enhancing Protective Efficacy of Poultry Vaccines through Targeted Delivery of Antigens to Antigen-Presenting Cells

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 75 ◽  
Author(s):  
Angita Shrestha ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal
Keyword(s):  
B Cells ◽  
Avian Influenza ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Antigen Presenting Cells ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Capture Process ◽  
Selective Delivery ◽  
Antigen Presenting

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.

scholarly journals Glycine at Position 622 in PB1 Contributes to the Virulence of H5N1 Avian Influenza Virus in Mice

2015 ◽  
Vol 90 (4) ◽  
pp. 1872-1879 ◽  
Author(s):  
Xiaoxiao Feng ◽  
Zeng Wang ◽  
Jianzhong Shi ◽  
Guohua Deng ◽  
Huihui Kong ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Aspartic Acid ◽  
H5n1 Virus ◽  
Genetic Basis ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Live Attenuated Vaccine ◽  
H5n1 Influenza ◽  
H5n1 Avian Influenza

ABSTRACTWe isolated two H5N1 viruses, A/duck/Hunan/S4020/2008 (DK/08) and A/chicken/Guangxi/S2039/2009 (CK/09), from live-bird markets during routine surveillance and found that these two viruses are genetically similar but differ in their replication and virulence in mice. The CK/09 virus is lethal for mice with a 50% mouse lethal dose (MLD50) of 1.6 log1050% egg infectious doses (EID50), whereas the DK/08 virus is nonpathogenic for mice with an MLD50value of 6.2 log10EID50. We explored the genetic basis of the virulence difference of these two viruses by generating a series of reassortant viruses and mutants in the lethal virus CK/09 background and evaluating their virulence in mice. We found that the PB1 gene of the DK/08 virus dramatically attenuated the virulence of the CK/09 virus and that the amino acid at position 622 in PB1 made an important contribution. We further demonstrated that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impaired the binding of PB1 to viral RNA, thereby dramatically decreasing the polymerase activity and attenuating H5N1 virus virulence in mice. Our results identify a novel virulence-related marker of H5N1 influenza viruses and provide a new target for live attenuated vaccine development.IMPORTANCEH5N1 avian influenza viruses have caused the deaths of nearly 60% of the humans that they have infected since 1997 and clearly represent a threat to public health. A thorough understanding of the genetic basis of virulence determinants will provide important insights for antiviral drug and live attenuated vaccine development. Several virulence-related markers in the PB2, PA, M1, and NS1 proteins of H5N1 viruses have been identified. In this study, we isolated two H5N1 avian influenza viruses that are genetically similar but differ in their virulence in mice, and we identified a new virulence-related marker in the PB1 gene. We found that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impairs the binding of PB1 to viral RNA, thereby attenuating H5N1 virus virulence in mice. This newly identified virulence-related marker could be applied to the development of live attenuated vaccines against H5N1 influenza.

Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates

2021 ◽  
Vol 13 (583) ◽  
pp. eabe5449
Author(s):  
Nicole Darricarrère ◽  
Yu Qiu ◽  
Masaru Kanekiyo ◽  
Adrian Creanga ◽  
Rebecca A. Gillespie ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Nonhuman Primates ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Gene Families ◽  
Influenza Viruses ◽  
Public Health Importance ◽  
Water Emulsion

Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus–associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

scholarly journals Inactivation of avian influenza viruses by hydrostatic pressure as a potential vaccine development approach

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Shana Priscila Coutinho Barroso ◽  
Ana Clara Vicente dos Santos ◽  
Patrícia Souza dos Santos ◽  
José Nelson dos Santos Silva Couceiro ◽  
Davis Fernandes Ferreira ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Avian Influenza ◽  
Influenza A ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Influenza Viruses ◽  
Structure Morphology ◽  
Potential Vaccine ◽  
Development Approach ◽  
H3n8 Virus

Vaccines are a recommended strategy for controlling influenza A infections in humans and animals. Here, we describe the effects of hydrostatic pressure on the structure, morphology and functional characteristics of avian influenza A H3N8 virus. The effect of hydrostatic pressure for 3 h on H3N8 virus revealed that the particles were resistant to this condition, and the virus displayed only a discrete conformational change. We found that pressure of 3 kbar applied for 6 h was able to inhibit haemagglutination and infectivity while virus replication was no longer observed, suggesting that full virus inactivation occurred at this point. However, the neuraminidase activity was not affected at this approach suggesting the maintenance of neutralizing antibody epitopes in this key antigen. Our data bring important information for the area of structural virology of enveloped particles and support the idea of applying pressure-induced inactivation as a tool for vaccine production.

scholarly journals A Replication-Defective Influenza Virus Harboring H5 and H7 Hemagglutinins Provides Protection against H5N1 and H7N9 Infection in Mice

2020 ◽  
Author(s):  
Xingui Tian ◽  
Shelby Landreth ◽  
Yao Lu ◽  
Kannupriya Pandey ◽  
Yan Zhou
Keyword(s):  
Avian Influenza ◽  
Immune Responses ◽  
Vaccine Candidate ◽  
Mortality Rates ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
H7n9 Virus ◽  
Complete Protection ◽  
Virus Challenge ◽  
Ha Gene

The recent highly pathogenic avian influenza (HPAI) H5N1 and H7N9 viruses have caused hundreds of human infections with high mortality rates. Although H5N1 and H7N9 viruses have been mainly limited to avian species, there is high potential for these viruses to acquire human-to-human transmission and initiate a pandemic. A highly safe and effective vaccine is needed to protect against a potential H5N1 or H7N9 influenza pandemic. Here, we report the generation and evaluation of two reassortant influenza viruses, PR8-H5-H7NA and PR8-H7-H5NA. These viruses contain six internal segments from A/Puerto Rico/8/1934 (PR8), the HA segment from either A/Alberta/01/2014 (H5N1) [AB14 (H5N1)] or A/British Columbia/01/2015 (H7N9) [BC15 (H7N9)], and a chimeric NA segment with either the BC15 (H7N9) HA gene or the AB14 (H5N1) HA gene flanked by the NA packaging signals of PR8. These viruses expressed both H5 and H7 HAs in infected cells, replicated to high titres when exogenous NA was added to the culture medium in vitro, and were replication-defective and non-virulent when administered intranasally in mice. Moreover, intranasal vaccination with PR8-H5-H7NA elicited robust immune responses to both H5 and H7 viruses, conferring complete protection against both AB14 (H5N1) and BC15 (H7N9) challenges in mice. Conversely, vaccination with PR8-H7-H5NA only elicited robust immune responses towards the H7 virus, which conferred complete protection against BC15 (H7N9) but not against AB14 (H5N1) in mice. Therefore, PR8-H5-H7NA has strong potential to serve as a vaccine candidate against both H5 and H7 subtypes of influenza viruses. Importance Avian influenza H5N1 and H7N9 viruses infected human with high mortality rates. A highly safe and effective vaccine is needed to protect against a potential pandemic. We generated and evaluated two reassortant influenza viruses, PR8-H5-H7NA and PR8-H7-H5NA as vaccine candidates. Each virus contains one type of HA in segment 4 and the other subtype of HA in segment 6, thus expressing both H5 and H7 subtypes of HA molecule. The viruses’ replication is dependent in the addition of exogenous NA in cell culture, and are replication-defective in vivo. Vaccination of PR8-H5-H7NA virus confers protection to both H5N1 and H7N9 virus challenge; conversely, vaccination of PR8-H7-H5NA only provides protection to H7N9 virus challenge. Our data revealed when engineering such virus, the H5 or H7 HA in segment 6 affects the immunogenicity. PR8-H5-H7NA has strong potential to serve as a vaccine candidate against both H5 and H7 subtypes of influenza viruses.

scholarly journals Emerging Respiratory Viruses: Challenges and Vaccine Strategies

2006 ◽  
Vol 19 (4) ◽  
pp. 614-636 ◽  
Author(s):  
Laura Gillim-Ross ◽  
Kanta Subbarao
Keyword(s):  
Avian Influenza ◽  
Viral Infection ◽  
Viral Infections ◽  
Vaccine Development ◽  
Respiratory Viruses ◽  
Lessons Learned ◽  
Influenza Viruses ◽  
Viral Pathogens ◽  
Current Vaccine ◽  
The Many

SUMMARY The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from current vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed.

scholarly journals Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1034
Author(s):  
Ahmed O. Shalash ◽  
Luke Becker ◽  
Jieru Yang ◽  
Paul Giacomin ◽  
Mark Pearson ◽  
...  
Keyword(s):  
Immune Response ◽  
Worm Burden ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Digestive Enzyme ◽  
Peptide Vaccine ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
Hookworm Infection ◽  
Linear Arrangement

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL10. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.

scholarly journals The Multifaceted Zoonotic Risk of H9N2 Avian Influenza

2018 ◽  
Vol 5 (4) ◽  
pp. 82 ◽  
Author(s):  
Elizabeth Pusch ◽  
David Suarez
Keyword(s):  
Avian Influenza ◽  
Severe Pneumonia ◽  
Cell Receptor ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Upper Respiratory Tract ◽  
Zoonotic Risk ◽  
Occupationally Exposed ◽  
Upper Respiratory ◽  
Almost All

Poultry-adapted H9N2 avian influenza viruses (AIVs) are commonly found in many countries in Asia, the Middle East, Africa, and Europe, and although classified as low pathogenic viruses, they are an economically important disease. Besides the importance of the disease in the poultry industry, some H9N2 AIVs are also known to be zoonotic. The disease in humans appears to cause primarily a mild upper respiratory disease, and doesn’t cause or only rarely causes the severe pneumonia often seen with other zoonotic AIVs like H5N1 or H7N9. Serologic studies in humans, particularly in occupationally exposed workers, show a large number of people with antibodies to H9N2, suggesting infection is commonly occurring. Of the four defined H9N2 poultry lineages, only two lineages, the G1 and the Y280 lineages, are associated with human infections. Almost all of the viruses from humans have a leucine at position 226 (H3 numbering) of the hemagglutinin associated with a higher affinity of binding with α2,6 sialic acid, the host cell receptor most commonly found on glycoproteins in the human upper respiratory tract. For unknown reasons there has also been a shift in recent years of poultry viruses in the G1 and Y280 lineages to also having leucine instead of glutamine, the amino acid found in most avian viruses, at position 226. The G1 and Y280 poultry lineages because of their known ability to infect humans, the high prevalence of the virus in poultry in endemic countries, the lack of antibody in most humans, and the shift of poultry viruses to more human-like receptor binding makes these viruses a human pandemic threat. Increased efforts for control of the virus, including through effective vaccine use in poultry, is warranted for both poultry and public health goals.

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