Next Article in Journal
Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies
Next Article in Special Issue
Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults
Previous Article in Journal
Universal Single-Dose Vaccination against Hepatitis A in Children in a Region of High Endemicity
Previous Article in Special Issue
Recombinant Enterovirus 71 Viral Protein 1 Fused to a Truncated Newcastle Disease Virus NP (NPt) Carrier Protein
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Vaccines
Volume 8
Issue 4
10.3390/vaccines8040781
vaccines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin

by
Se-Hee An
1,2,
Seung-Min Hong
1,2,
Seung-Eun Son
1,
Jin-Ha Song
1,
Chung-Young Lee
1,
Jun-Gu Choi
3,
Youn-Jeong Lee
3,
Jei-Hyun Jeong
4,
Jun-Beom Kim
4,
Chang-Seon Song
4,
Jae-Hong Kim
2,
Kang-Seuk Choi
1,2 and
Hyuk-Joon Kwon
2,5,*
1
Laboratory of Avian Diseases, College of veterinary medicine, Seoul National University, Seoul 08826, Korea
2
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
3
Avian Disease Division, Animal and Plant Quarantine Agency, 177, Hyeoksin 8-ro, Gyeongsangbuk-do 39660, Korea
4
Laboratory of Avian Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
5
Farm Animal Clinical Training and Research Center (FACTRC), Institutes of Green-bio Science & Technology, Seoul National University, Kangwon-do 25354, Korea
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(4), 781; https://doi.org/10.3390/vaccines8040781
Submission received: 25 November 2020 / Revised: 16 December 2020 / Accepted: 17 December 2020 / Published: 20 December 2020
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
Browse Figures
Review Reports Versions Notes

Abstract

Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in embryonated chicken eggs-based vaccine production system, they need to be improved in terms of immunogenicity and potential mammalian pathogenicity. We replaced the PB2 gene alone or the PB2 (polymerase basic protein 2), NP (nucleoprotein), M (matrix protein) and NS (non-structural protein) genes together in the PR8 strain with corresponding genes from AIVs with low pathogenicity to remove mammalian pathogenicity and to match CD8+ T cell epitopes with contemporary HPAI viruses, respectively, without loss of viral fitness. Additionally, we tested the effect of the H103Y mutation of hemagglutinin (HA) on antigen productivity, mammalian pathogenicity and heat/acid stability. The replacement of PB2 genes and the H103Y mutation reduced the mammalian pathogenicity but increased the antigen productivity of the recombinant vaccine strains. The H103Y mutation increased heat stability but unexpectedly decreased acid stability, probably resulting in increased activation pH for HA. Interestingly, vaccination with inactivated recombinant virus with replaced NP, M and NS genes halted challenge virus shedding earlier than the recombinant vaccine without internal genes replacement. In conclusion, we successfully generated recombinant clade 2.3.4.4c H5N6 vaccine strains that were less pathogenic to mammals and more productive and heat stable than conventional PR8-derived recombinant strains by optimization of internal genes and the H103Y mutation of HA.
Keywords: clade 2.3.4.4c H5N6 vaccine; antigen productivity; T cell epitopes; heat/acid stability clade 2.3.4.4c H5N6 vaccine; antigen productivity; T cell epitopes; heat/acid stability

Share and Cite

MDPI and ACS Style

An, S.-H.; Hong, S.-M.; Son, S.-E.; Song, J.-H.; Lee, C.-Y.; Choi, J.-G.; Lee, Y.-J.; Jeong, J.-H.; Kim, J.-B.; Song, C.-S.; et al. Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin. Vaccines 2020, 8, 781. https://doi.org/10.3390/vaccines8040781

AMA Style

An S-H, Hong S-M, Son S-E, Song J-H, Lee C-Y, Choi J-G, Lee Y-J, Jeong J-H, Kim J-B, Song C-S, et al. Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin. Vaccines. 2020; 8(4):781. https://doi.org/10.3390/vaccines8040781

Chicago/Turabian Style

An, Se-Hee, Seung-Min Hong, Seung-Eun Son, Jin-Ha Song, Chung-Young Lee, Jun-Gu Choi, Youn-Jeong Lee, Jei-Hyun Jeong, Jun-Beom Kim, Chang-Seon Song, and et al. 2020. "Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin" Vaccines 8, no. 4: 781. https://doi.org/10.3390/vaccines8040781

APA Style

An, S.-H., Hong, S.-M., Son, S.-E., Song, J.-H., Lee, C.-Y., Choi, J.-G., Lee, Y.-J., Jeong, J.-H., Kim, J.-B., Song, C.-S., Kim, J.-H., Choi, K.-S., & Kwon, H.-J. (2020). Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin. Vaccines, 8(4), 781. https://doi.org/10.3390/vaccines8040781

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop