Citation

  • Authors: Darricarrere, 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.
  • Year: 2018
  • Journal: J Virol
  • Applications: in vitro / DNA / FectoPRO
  • Cell type: Expi293F
    Description: Human embryonic kidney Fibroblast
    Known as: Expi 293-F, Expi, HEK-293 Expi

Abstract

The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Though 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 (1). To determine whether combinations of specific H1 HA antigens stimulate immune responses that protect against diverse H1 influenza, 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) or COBRA-X6 and P1 elicited neutralization against diverse strains, and a combination of these three wildtype HA- or two COBRA HA-nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may potentially 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.

Pubmed