Alum adjuvant rescues HPAI vaccine immunogenicity and survival in BALB/c mice following H5N1 infection (113.30)

Abstract

Abstract Highly pathogenic avian influenza (HPAI) is an emerging infectious virus with an approximate 60% fatality rate in humans. In the United States, a vaccine for H5N1 has been developed and stockpiled in case of a pandemic. This vaccine demonstrated low immunogenicity in human clinical trials with only 22% of recipients developing protective antibody titers. Previous studies using a lethal challenge ferret model have shown that supplementing the H5N1 vaccine with an alum adjuvant can improve immunogenicity and survival. We developed a lethal challenge mouse model of H5N1 vaccination to examine differences in innate immune responses to the vaccine alone or in the presence of an alum adjuvant. Mice treated with the adjuvanted vaccine showed significantly lower weight loss and higher survival than mice treated with the nonadjuvanted vaccine. Further, mice treated with adjuvanted vaccine had higher neutralizing antibody titers when compared to mice that received the nonadjuvanted vaccine. In vitro, dendritic cells (DCs) cultured with the adjuvanted vaccine had increased expression of the activation markers CD40 and CD86 compared to DCs treated with the nonadjuvanted vaccine. Interestingly, neither treatment induced activation of Toll-like receptors or the production of cytokines IL-6, IL-12, or TNF-α. Taken together, our results suggest that the alum adjuvant rescues immunogenicity and improves survival in the host.