Cross-protection by inactivated H5 prepandemic vaccine seed strains against diverse Goose/Guangdong lineage H5N1 highly pathogenic avian influenza viruses

Authors: CRIADO, MIRIA - Orise Fellow; SA-E-SILVA, MARIANA - Boehringer Ingelheim; LEE, DONG-HUN - University Of Connecticut; SALGE, CAROLINA - Wake Forest University; Spackman, Erica; DONIS, RUBEN - Beijing Center For Diseases Prevention And Control; WAN, XIU-FENG - University Of Missouri; Swayne, David

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/22/2020
Publication Date: 11/23/2020
Citation: Criado, M.F., Sa-E-Silva, M., Lee, D., Salge, C.A., Spackman, E., Donis, R., Wan, X., Swayne, D.E. 2020. Cross-protection by inactivated H5 prepandemic vaccine seed strains against diverse Goose/Guangdong lineage H5N1 highly pathogenic avian influenza viruses. Journal of Virology. 94(24):e00720-20. https://doi.org/10.1128/JVI.00720-20.
DOI: https://doi.org/10.1128/JVI.00720-20

Interpretive Summary: The H5N1 Goose/Guangdong lineage (Gs/GD) lineage of the highly pathogenic avian influenza (HPAI) virus is widespread, producing infections in poultry, wild birds or humans. These viruses are rapidly changing by mutation leading to inadequate protection by the available poultry and human pre-pandemic vaccines. This study aimed to determine the protective ability for six inactivated H5N1 vaccines, available in pre-pandemic preparedness vaccine bank, against eight H5N1 HPAI field viruses using a chicken model. Nearly half (47.92%) of the forty-eight combinations of vaccine/challenge viruses used in our study were able to provide bird protection against mortality and clinical signs. The comparison across all protection parameters, homologous or closely related vaccine/challenge viruses had the best protection. Therefore, this study highlights the virus diversity, complexity of the immune response, and the importance of strain selection for vaccines to control HPAIV H5N1.

Technical Abstract: The highly pathogenic avian influenza virus (HPAIV) H5N1 Goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world, and has caused lethal, sporadic infections in humans. Vaccines are important in HPAI control, both for poultry and pre-pandemic preparedness in humans. This study assessed, with a chicken challenge model, the protection against mortality with field H5N1 Gs/GD viruses by inactivated pre-pandemic vaccine seed strains. Nearly half (47.92%) of the forty-eight combinations of vaccine/challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death time (MDT) and the virus shedding titers were significantly lower compared to the sham group (p= 0.05). The antibody titers in the pre-challenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination inhibiting (HI) antibodies against homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters, homologous or closely related vaccine and challenge viruses, gave the best protection. Through additional analysis, we identified a pattern of epitopes substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.