Computationally optimized broadly reactive vaccine based upon swine H1N1 influenza hemagglutinin sequences protects against both swine and human isolated viruses

Amanda L Skarlupka; Simon O Owino; Lui P Suzuki-Williams; Corey J Crevar; Donald M Carter; Ted M Ross

doi:10.1080/21645515.2019.1653743

Computationally optimized broadly reactive vaccine based upon swine H1N1 influenza hemagglutinin sequences protects against both swine and human isolated viruses

Hum Vaccin Immunother. 2019;15(9):2013-2029. doi: 10.1080/21645515.2019.1653743.

Authors

Amanda L Skarlupka¹, Simon O Owino¹, Lui P Suzuki-Williams¹, Corey J Crevar², Donald M Carter^{1

3}, Ted M Ross^{1

3}

Affiliations

¹ Center for Vaccines and Immunology, University of Georgia , Athens , GA , USA.
² Vaccine and Gene Therapy Institute of Florida , Port St. Lucie , FL , USA.
³ Department of Infectious Diseases, University of Georgia , Athens , GA , USA.

Abstract

Swine H1 influenza viruses were stable within pigs for nearly 70 years until in 1998 when a classical swine virus reassorted with avian and human influenza viruses to generate the novel triple reassortant H1N1 strain that eventually led to the 2009 influenza pandemic. Previously, our group demonstrated broad protection against a panel of human H1N1 viruses using HA antigens derived by the COBRA methodology. In this report, the effectiveness of COBRA HA antigens (SW1, SW2, SW3 and SW4), which were designed using only HA sequences from swine H1N1 and H1N2 isolates, were tested in BALB/c mice. The effectiveness of these vaccines were compared to HA sequences designed using both human and swine H1 HA sequences or human only sequences. SW2 and SW4 elicited antibodies that detected the pandemic-like virus, A/California/07/2009 (CA/09), had antibodies with HAI activity against almost all the classical swine influenza viruses isolated from 1973-2015 and all of the Eurasian viruses in our panel. However, sera collected from mice vaccinated with SW2 or SW4 had HAI activity against ~25% of the human seasonal-like influenza viruses isolated from 2009-2015. In contrast, the P1 COBRA HA vaccine (derived from both swine and human HA sequences) elicited antibodies that had HAI activity against both swine and human H1 viruses and protected against CA/09 challenge, but not a human seasonal-like swine H1N2 virus challenge. However, the SW1 vaccine protected against this challenge as well as the homologous vaccine. These results support the idea that a pan-swine-human H1 influenza virus vaccine is possible.

Keywords: COBRA; H1N1; hemagglutination-inhibition; influenza; mice.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / blood*
Antigens, Viral / genetics
Antigens, Viral / immunology
Computers, Molecular
Female
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / immunology*
Humans
Influenza A Virus, H1N1 Subtype
Influenza Vaccines / administration & dosage
Influenza Vaccines / immunology*
Influenza, Human / prevention & control*
Influenza, Human / virology
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections / prevention & control*
Orthomyxoviridae Infections / virology
Swine
Vaccines, Virus-Like Particle / immunology

Substances

Antibodies, Viral
Antigens, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
Vaccines, Virus-Like Particle

Grants and funding

This work was funded, in part, by the University of Georgia (UGA) (MRA-001). In addition, TMR is supported by the Georgia Research Alliance as an Eminent Scholar; Georgia Research Alliance [GRA-001];