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Development of influenza H7N9 virus like particle (VLP) vaccine: homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus.
Vaccine. 2013 Sep 13; 31(40):4305-13.V

Abstract

The recent emergence of severe human illness caused by avian-origin influenza A(H7N9) viruses in China has precipitated a global effort to rapidly develop and test vaccine candidates. To date, non-A(H7N9) H7 subtype influenza vaccine candidates have been poorly immunogenic and difficulties in production of A(H7N9) virus seed strains have been encountered. A candidate recombinant A(H7N9) vaccine consisting of full length, unmodified hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) were cloned into a baculovirus vector. Baculovirus infected Spodoptera frugiperda (Sf9) insect cells secreted virus like particles (VLP) composed of HA, NA, and M1 that resemble mature influenza virions. Genetic construction of vaccine from acquisition of an H7N9 genomic sequence to production of A(H7N9) VLP occurred in 26 days. The immunogenicity and efficacy of A/Anhui/1/2013 (H7N9) VLP vaccine administered on days 0 and 14 were evaluated in a lethal wild-type challenge Balb/c mouse model. Control groups included a non-homologous H7 vaccine (A/chicken/Jalisco/CPA1/2012 (H7N3)-VLP), and A/Indonesia/05/2005 (H5N1)-VLP, or placebo. All vaccines were administered with or without ISCOMATRIX. A(H7N9) VLP elicited hemagglutination-inhibition (HAI) antibody titers of ≥ 1:64 against the homologous virus, cross-reactive HAI against the heterologous A(H7N3), and 3- to 4-fold higher HAI responses in corresponding ISCOMATRIX subgroups. Similarly, all doses of H7N9 VLP elicited anti-neuraminidase (NA) antibody, with 3- to 4-fold higher responses measured in the corresponding ISCOMATRIX subgroups. The non-homologous H7 vaccine induced both H7N3 and H7N9 HAI but no N9 anti-NA antibodies. A lethal murine wild-type A/Anhui/1/2013 (H7N9) challenge demonstrated 100% survival of all animals receiving A(H7N9) and A(H7N3) vaccine, versus 0% survival in A(H5N1) vaccine and placebo groups. Together, the data demonstrate that recombinant H7N9 vaccine can be rapidly developed that was immunogenic and efficacious supporting testing in man as a pandemic influenza H7N9 vaccine candidate.

Authors+Show Affiliations

Novavax, Inc., 9920 Belward Campus Drive, Rockville, MD 20850, USA. gsmith@novavax.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23891795

Citation

Smith, Gale E., et al. "Development of Influenza H7N9 Virus Like Particle (VLP) Vaccine: Homologous A/Anhui/1/2013 (H7N9) Protection and Heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) Cross-protection in Vaccinated Mice Challenged With H7N9 Virus." Vaccine, vol. 31, no. 40, 2013, pp. 4305-13.
Smith GE, Flyer DC, Raghunandan R, et al. Development of influenza H7N9 virus like particle (VLP) vaccine: homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus. Vaccine. 2013;31(40):4305-13.
Smith, G. E., Flyer, D. C., Raghunandan, R., Liu, Y., Wei, Z., Wu, Y., Kpamegan, E., Courbron, D., Fries, L. F., & Glenn, G. M. (2013). Development of influenza H7N9 virus like particle (VLP) vaccine: homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus. Vaccine, 31(40), 4305-13. https://doi.org/10.1016/j.vaccine.2013.07.043
Smith GE, et al. Development of Influenza H7N9 Virus Like Particle (VLP) Vaccine: Homologous A/Anhui/1/2013 (H7N9) Protection and Heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) Cross-protection in Vaccinated Mice Challenged With H7N9 Virus. Vaccine. 2013 Sep 13;31(40):4305-13. PubMed PMID: 23891795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of influenza H7N9 virus like particle (VLP) vaccine: homologous A/Anhui/1/2013 (H7N9) protection and heterologous A/chicken/Jalisco/CPA1/2012 (H7N3) cross-protection in vaccinated mice challenged with H7N9 virus. AU - Smith,Gale E, AU - Flyer,David C, AU - Raghunandan,Ramadevi, AU - Liu,Ye, AU - Wei,Ziping, AU - Wu,Yingyun, AU - Kpamegan,Eloi, AU - Courbron,Denise, AU - Fries,Louis F,3rd AU - Glenn,Gregory M, Y1 - 2013/07/26/ PY - 2013/06/18/received PY - 2013/07/08/revised PY - 2013/07/17/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/4/1/medline KW - H7N9 KW - Hemagglutinin KW - Influenza KW - Pandemic KW - Vaccine KW - Virus like particle SP - 4305 EP - 13 JF - Vaccine JO - Vaccine VL - 31 IS - 40 N2 - The recent emergence of severe human illness caused by avian-origin influenza A(H7N9) viruses in China has precipitated a global effort to rapidly develop and test vaccine candidates. To date, non-A(H7N9) H7 subtype influenza vaccine candidates have been poorly immunogenic and difficulties in production of A(H7N9) virus seed strains have been encountered. A candidate recombinant A(H7N9) vaccine consisting of full length, unmodified hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) were cloned into a baculovirus vector. Baculovirus infected Spodoptera frugiperda (Sf9) insect cells secreted virus like particles (VLP) composed of HA, NA, and M1 that resemble mature influenza virions. Genetic construction of vaccine from acquisition of an H7N9 genomic sequence to production of A(H7N9) VLP occurred in 26 days. The immunogenicity and efficacy of A/Anhui/1/2013 (H7N9) VLP vaccine administered on days 0 and 14 were evaluated in a lethal wild-type challenge Balb/c mouse model. Control groups included a non-homologous H7 vaccine (A/chicken/Jalisco/CPA1/2012 (H7N3)-VLP), and A/Indonesia/05/2005 (H5N1)-VLP, or placebo. All vaccines were administered with or without ISCOMATRIX. A(H7N9) VLP elicited hemagglutination-inhibition (HAI) antibody titers of ≥ 1:64 against the homologous virus, cross-reactive HAI against the heterologous A(H7N3), and 3- to 4-fold higher HAI responses in corresponding ISCOMATRIX subgroups. Similarly, all doses of H7N9 VLP elicited anti-neuraminidase (NA) antibody, with 3- to 4-fold higher responses measured in the corresponding ISCOMATRIX subgroups. The non-homologous H7 vaccine induced both H7N3 and H7N9 HAI but no N9 anti-NA antibodies. A lethal murine wild-type A/Anhui/1/2013 (H7N9) challenge demonstrated 100% survival of all animals receiving A(H7N9) and A(H7N3) vaccine, versus 0% survival in A(H5N1) vaccine and placebo groups. Together, the data demonstrate that recombinant H7N9 vaccine can be rapidly developed that was immunogenic and efficacious supporting testing in man as a pandemic influenza H7N9 vaccine candidate. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/23891795/Development_of_influenza_H7N9_virus_like_particle__VLP__vaccine:_homologous_A/Anhui/1/2013__H7N9__protection_and_heterologous_A/chicken/Jalisco/CPA1/2012__H7N3__cross_protection_in_vaccinated_mice_challenged_with_H7N9_virus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(13)00987-0 DB - PRIME DP - Unbound Medicine ER -