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Development of a Pan-H1 Influenza Vaccine.
J Virol. 2018 11 15; 92(22)JV

Abstract

The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine.IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.

Links

Authors+Show Affiliations

Darricarrère N

Sanofi, Cambridge, Massachusetts, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Sanofi, Cambridge, Massachusetts, USA.

Sanofi, Cambridge, Massachusetts, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Sanofi Pasteur Biologics, Cambridge, Massachusetts, USA.

Sanofi, Cambridge, Massachusetts, USA Chih-Jen.Wei@Sanofi.com Gary.Nabel@sanofi.com.

Sanofi, Cambridge, Massachusetts, USA Chih-Jen.Wei@Sanofi.com Gary.Nabel@sanofi.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30185594

Citation

Darricarrère, Nicole, et al. "Development of a Pan-H1 Influenza Vaccine." Journal of Virology, vol. 92, no. 22, 2018.

Darricarrère N, Pougatcheva S, Duan X, et al. Development of a Pan-H1 Influenza Vaccine. J Virol. 2018;92(22).

Darricarrère, N., Pougatcheva, S., Duan, X., Rudicell, R. S., Chou, T. H., DiNapoli, J., Ross, T. M., Alefantis, T., Vogel, T. U., Kleanthous, H., Wei, C. J., & Nabel, G. J. (2018). Development of a Pan-H1 Influenza Vaccine. Journal of Virology, 92(22). https://doi.org/10.1128/JVI.01349-18

Darricarrère N, et al. Development of a Pan-H1 Influenza Vaccine. J Virol. 2018 11 15;92(22) PubMed PMID: 30185594.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Development of a Pan-H1 Influenza Vaccine. AU - Darricarrère,Nicole, AU - Pougatcheva,Svetlana, AU - Duan,Xiaochu, AU - Rudicell,Rebecca S, AU - Chou,Te-Hui, AU - DiNapoli,Joshua, AU - Ross,Ted M, AU - Alefantis,Tim, AU - Vogel,Thorsten U, AU - Kleanthous,Harry, AU - Wei,Chih-Jen, AU - Nabel,Gary J, Y1 - 2018/10/29/ PY - 2018/08/17/received PY - 2018/08/22/accepted PY - 2018/9/7/pubmed PY - 2019/9/4/medline PY - 2018/9/7/entrez KW - H1N1 KW - H1N1 influenza KW - HA-ferritin nanoparticles KW - influenza vaccines KW - vaccines JF - Journal of virology JO - J Virol VL - 92 IS - 22 N2 - The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine.IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/30185594/Development_of_a_Pan_H1_Influenza_Vaccine_ DB - PRIME DP - Unbound Medicine ER -