Scientific Publications by FDA Staff

J Virol 2012 Nov;86(22):12283-93

Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild type H5N1 influenza challenge and control viral loads better than subunit H5N1 vaccine by eliciting high affinity antibodies.

Verma S, Dimtrova M, Munjal A, Fontana J, Crevar CJ, Carter DM, Ross TM, Khurana S, Golding H

Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In the current study we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1, or SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (but not monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection from lethality and morbidity from homologous and heterologous HP-H5N1 challenge. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher serum antibody binding to HA1 with stronger avidity & better IgG/IgM ratio compared to monomeric HA1 and SU-H5N1 vaccine using surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1 vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses as measured by SPR. This is the first study to show the role of antibody avidity to the HA1 globular head domain in reduction of viral loads in upper respiratory tract, which could significantly reduce viral transmission.