Designing a multi-epitope vaccine to provoke the robust immune response against influenza A H7N9

AbstractA new strain of Influenza A Virus (IAV), so-called "H7N9 Avian Influenza", is the first strain of this virus in which a human is infected by transmitting the N9 of influenza virus. Although continuous human-to-human transmission has not been reported, the occurrence of various H7N9-associated epidemics and the lack of production of strong antibodies against H7N9 in humans warn of the potential for H7N9 to become a new pandemic. Therefore, the need for effective vaccination against H7N9 as a life-threatening viral pathogen has become a major concern. The current study reports the design of a multi-epitope vaccine against Hemagglutinin (HA) and Neuraminidase (NA) proteins of H7N9 Influenza A virus by prediction of Cytotoxic T lymphocyte (CTL), Helper T lymphocyte (HTL), IFN-γ and B-cell epitopes. Human β-defensin-3 (HβD-3) and pan HLA DR-binding epitope (PADRE) sequence were considered as adjuvant. EAAAK, AAY, GPGPG, HEYGAEALERAG, KK and RVRR linkers were used as a connector for epitopes. The final construct contained 777 amino acids that are expected to be a recombinant protein of about ~ 86.38 kDa with antigenic and non-allergenic properties after expression. Modeled protein analysis based on the tertiary structure validation, docking studies, and molecular dynamics simulations results like Root-mean-square deviation (RMSD), Gyration, Root-mean-square fluctuation (RMSF) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) showed that this protein has a stable construct and capable of being in interaction with Toll-like receptor 7 (TLR7), TLR8 and m826 antibody. Analysis of the obtained data the demonstrates that suggested vaccine has the potential to induce the immune response by stimulating T and Bcells, and may be utilizable for prevention purposes against Avian Influenza A (H7N9).

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Modern application and prospects of the stable isotopes method for studying avian influenza A virus transmission in migratory birds

South of Russia ecology development ◽

10.18470/1992-1098-2019-3-92-100 ◽

2019 ◽

Vol 14 (3) ◽

pp. 92-100

Author(s):

O. R. Druzyaka ◽

A. V. Druzyaka ◽

M. A. Gulyaeva ◽

F. Huettmann ◽

A. M. Shestopalov

Keyword(s):

Stable Isotopes ◽

Avian Influenza ◽

Influenza A Virus ◽

Influenza A ◽

Bird Migration ◽

Migratory Birds ◽

Influenza Viruses ◽

Migration Routes ◽

Viral Pathogen ◽

Avian Influenza A Virus

Aim. The circulation and transmission of pathogens is a global biological phenomenon that is closely associated with bird migration. This analysis was carried out with the aim of understanding and assessing the prospects of using the stable isotope method to study the circulation and transmission of the avian influenza A virus via migratory birds. Discussion. Insufficient data on the distances of migration of infected birds and their interpopulational relationships leaves open the question of the transmission of highly pathogenic influenza viruses (HSV) in the wild bird population. A deeper study of the role of migrations in the spread of HSV may possibly allow the more effective investigation of the transmission of the viral pathogen between individuals at migration stopover sites and the clarification of global migration routes. New methodological approaches are providing a more complete picture of the geography and phenology of migrations, as well as of the consequences of migratory behavior for species biology. The study of the quantitative component of migratory flows based on the analysis of the content of stable isotopes (SIMS) in bird tissues seems very promising. This method is being applied to the solution of various environmental issues, including the study of animal migrations. Conclusion. Based on data from the scientific literature, it is shown that SIMS is promising for the clarification of bird migration routes and the quantification of their intensity. The resolving power of the method is sufficient to determine the migration pathways of carriers of viral pathogens on the scale of zoogeographic subdomains and in even further detail. However, to date, there have been few such studies: in Russia they have not been conducted at all. The increased use of the SIMS methodology may possibly reveal new ways in which viral infections are spread via birds.

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Immune response of mice to non-adapted avian influenza A virus

Acta Virologica ◽

10.4149/av_2015_04_350 ◽

2015 ◽

Vol 59 (04) ◽

pp. 350-359

Author(s):

A. STROPKOVSKÁ ◽

T. MIKUŠKOVÁ ◽

Z. BOBIŠOVÁ ◽

I. KOŠÍK ◽

V. MUCHA ◽

...

Keyword(s):

Immune Response ◽

Avian Influenza ◽

Influenza A Virus ◽

Influenza A ◽

Avian Influenza A Virus

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Links between fecal microbiota and the response to vaccination against influenza A virus in pigs

npj Vaccines ◽

10.1038/s41541-021-00351-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Marion Borey ◽

Fany Blanc ◽

Gaëtan Lemonnier ◽

Jean-Jacques Leplat ◽

Deborah Jardet ◽

...

Keyword(s):

Immune Response ◽

Influenza A Virus ◽

Influenza A ◽

16S Rrna Gene Sequencing ◽

Serum Levels ◽

Fecal Microbiota ◽

Rrna Gene ◽

Vaccine Response ◽

Specific Igg ◽

Rrna Gene Sequencing

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.

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Development of Neuraminidase Subtype-Specific Reference Antisera by Recombinant Protein Expressed in Baculovirus

Clinical and Vaccine Immunology ◽

10.1128/cvi.00385-12 ◽

2012 ◽

Vol 20 (2) ◽

pp. 140-145 ◽

Cited By ~ 3

Author(s):

Kyu-Jun Lee ◽

Jun-Gu Choi ◽

Hyun-Mi Kang ◽

Kwang-Il Kim ◽

Choi-Kyu Park ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Influenza A Virus ◽

Diagnostic Tests ◽

Influenza A ◽

Recombinant Baculovirus ◽

Cross Reactivity ◽

Specific Reference ◽

Simple Method ◽

Avian Influenza A Virus

ABSTRACTOutbreaks of avian influenza A virus infection, particularly the H5N1 strains that have affected birds and some humans for the past 15 years, have highlighted the need for increased surveillance and disease control. Such measures require diagnostic tests to detect and characterize the different subtypes of influenza virus. In the current study, a simple method for producing reference avian influenza virus antisera to be used in diagnostic tests was developed. Antisera of nine avian influenza A virus neuraminidases (NA) used for NA subtyping were produced using a recombinant baculovirus. The recombinant NA (rNA) proteins were expressed in Sf9 insect cells and inoculated intramuscularly into specific-pathogen-free chickens with the ISA70 adjuvant. The NA inhibition antibody titers of the rNA antiserum were in the ranges of 5 to 8 and 6 to 9 log2units after the primary and boost immunizations, respectively. The antisera were subtype specific, showing low cross-reactivity against every other NA subtype using the conventional thiobarbituric acid NA inhibition assay. These results suggest that this simple method for producing reference NA antisera without purification may be useful for the diagnosis and surveillance of influenza virus.

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Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽

10.3390/vaccines9060629 ◽

2021 ◽

Vol 9 (6) ◽

pp. 629

Author(s):

Megan M. Dunagan ◽

Kala Hardy ◽

Toru Takimoto

Keyword(s):

Immune Response ◽

Immune Responses ◽

Influenza A Virus ◽

Influenza A ◽

Human Populations ◽

Lymphocyte Migration ◽

Host Immune Responses ◽

Mhc Molecules ◽

The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

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Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

Journal of Virology ◽

10.1128/jvi.79.15.9926-9932.2005 ◽

2005 ◽

Vol 79 (15) ◽

pp. 9926-9932 ◽

Cited By ~ 70

Author(s):

Kyoko Shinya ◽

Masato Hatta ◽

Shinya Yamada ◽

Ayato Takada ◽

Shinji Watanabe ◽

...

Keyword(s):

Hong Kong ◽

Avian Influenza ◽

Influenza A Virus ◽

Influenza A ◽

Mainland China ◽

Virus Infections ◽

Influenza A Viruses ◽

H5n1 Avian Influenza Virus ◽

H5n1 Influenza ◽

Avian Influenza A Virus

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

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