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Split inactivated COBRA vaccine elicits protective antibodies against H1N1 and H3N2 influenza viruses.
PLoS One. 2018; 13(9):e0204284.Plos

Abstract

Development of broadly reactive or universal influenza vaccines will be a paradigm shifting event for the influenza vaccine field. These next generation vaccines could replace the current standard of care with vaccines that elicit broadly cross-protective immune responses. However, a variety of in vitro and in vivo models are necessary to make the best assessments of these vaccine formulations to determine their mechanisms of action, and allow for downselection of candidates prior to human clinical trials. Our group has developed the computationally optimized broadly reactive antigen (COBRA) technology to develop HA head-based strategies to elicit antibodies against H1, H3, and H5 influenza strains. These vaccines elicit broadly reactive antibody responses that neutralize not only historical and contemporary vaccine strains, but also co-circulating variants in mice. In this study, we used H1 and H3 HA antigens in a split, inactivated vaccine (IIV) formulation in combination with the AF03 squalene-in-water emulsion adjuvant in ferrets immunologically naïve to influenza virus. The H3 COBRA IIV vaccine T11 elicited antibodies with HAI activity against more H3N2 influenza strains compared to IIV expressing wild-type H3 HA antigens, except for IIV vaccines expressing the HA from A/Texas/50/2012 (Tx/12) virus. H1 COBRA IIV vaccines, P1 and X6, elicited antibodies that recognized a similar number of H1N1 viruses as those antibodies elicited by IIV expressing the A/California/07/2009 (CA/09) HA. Ferrets vaccinated with the P1 or X6 COBRA IIV were protected against CA/09 challege and cleared virus from the lungs of the ferrets, similar to ferrets vaccinated with the CA/09 IIV.

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Authors+Show Affiliations

Allen JD
Center for Vaccines and Immunology, University of Georgia, Athens, GA, United States of America.
Ray S
Sanofi-Pasteur, Inc., Cambridge, MA, United States of America.
Ross TM
Center for Vaccines and Immunology, University of Georgia, Athens, GA, United States of America. Department of Infectious Diseases, University of Georgia, Athens, GA, United States of America.

MeSH

AnimalsAntibodies, ViralFemaleFerretsHemagglutinin Glycoproteins, Influenza VirusInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza VaccinesVaccinationVaccines, Inactivated

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30265682

Citation

Allen, James D., et al. "Split Inactivated COBRA Vaccine Elicits Protective Antibodies Against H1N1 and H3N2 Influenza Viruses." PloS One, vol. 13, no. 9, 2018, pp. e0204284.
Allen JD, Ray S, Ross TM. Split inactivated COBRA vaccine elicits protective antibodies against H1N1 and H3N2 influenza viruses. PLoS One. 2018;13(9):e0204284.
Allen, J. D., Ray, S., & Ross, T. M. (2018). Split inactivated COBRA vaccine elicits protective antibodies against H1N1 and H3N2 influenza viruses. PloS One, 13(9), e0204284. https://doi.org/10.1371/journal.pone.0204284
Allen JD, Ray S, Ross TM. Split Inactivated COBRA Vaccine Elicits Protective Antibodies Against H1N1 and H3N2 Influenza Viruses. PLoS One. 2018;13(9):e0204284. PubMed PMID: 30265682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Split inactivated COBRA vaccine elicits protective antibodies against H1N1 and H3N2 influenza viruses. AU - Allen,James D, AU - Ray,Satyajit, AU - Ross,Ted M, Y1 - 2018/09/28/ PY - 2018/06/11/received PY - 2018/09/04/accepted PY - 2018/9/29/entrez PY - 2018/9/29/pubmed PY - 2019/3/2/medline SP - e0204284 EP - e0204284 JF - PloS one JO - PLoS One VL - 13 IS - 9 N2 - Development of broadly reactive or universal influenza vaccines will be a paradigm shifting event for the influenza vaccine field. These next generation vaccines could replace the current standard of care with vaccines that elicit broadly cross-protective immune responses. However, a variety of in vitro and in vivo models are necessary to make the best assessments of these vaccine formulations to determine their mechanisms of action, and allow for downselection of candidates prior to human clinical trials. Our group has developed the computationally optimized broadly reactive antigen (COBRA) technology to develop HA head-based strategies to elicit antibodies against H1, H3, and H5 influenza strains. These vaccines elicit broadly reactive antibody responses that neutralize not only historical and contemporary vaccine strains, but also co-circulating variants in mice. In this study, we used H1 and H3 HA antigens in a split, inactivated vaccine (IIV) formulation in combination with the AF03 squalene-in-water emulsion adjuvant in ferrets immunologically naïve to influenza virus. The H3 COBRA IIV vaccine T11 elicited antibodies with HAI activity against more H3N2 influenza strains compared to IIV expressing wild-type H3 HA antigens, except for IIV vaccines expressing the HA from A/Texas/50/2012 (Tx/12) virus. H1 COBRA IIV vaccines, P1 and X6, elicited antibodies that recognized a similar number of H1N1 viruses as those antibodies elicited by IIV expressing the A/California/07/2009 (CA/09) HA. Ferrets vaccinated with the P1 or X6 COBRA IIV were protected against CA/09 challege and cleared virus from the lungs of the ferrets, similar to ferrets vaccinated with the CA/09 IIV. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/30265682/Split_inactivated_COBRA_vaccine_elicits_protective_antibodies_against_H1N1_and_H3N2_influenza_viruses_ DB - PRIME DP - Unbound Medicine ER -