AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization

Abstract

Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced antibody epitope diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains.

Influenza: understanding the mechanisms of vaccine-boosting additives

Adjuvant AS03 improves a bird flu vaccine’s ability to recognize and bind to virion targets. Avian influenza viruses are considered a pandemic threat, and vaccines made from inactivated virus are limited in their efficacy. However, adjuvants such as AS03 have the ability to augment a host’s immunity, prompting Surender Khurana and colleagues from the United States’ Food and Drug Administration to investigate how. In an H5N1 vaccine trial, researchers found that AS03 improved immune responses by increasing the degree, diversity, and intensity of antibody binding to viral surface proteins, which likely caused the observed increase in the neutralization of the virus tested as well as efficacy against other H5N1 strains. The AS03-adjuvanted vaccine did not neutralize seasonal H1N1 influenza strains. This study may inform future vaccine development efforts by partially illuminating the effects of AS03.