AVIAN INFLUENZA VIRUS: THE NEXT PANDEMIC?

Abstract

Novel avian influenza viruses continue to circulate in animal species around the world and show a propensity to reassort and acquire virulence factors, which raises the concern that these viruses may adapt to humans. Pandemic preparedness has relied heavily on vaccine stockpiles. However, avian influenza strains genetically drift over time, and stockpiled vaccines often fail to elicit protective immunity for these genetic variants. Various strategies can help overcome immune imprinting and immunological hyporeactivity as well as broaden the immune response to variant viruses. Adjuvants remain a key strategy for improving the immunological response to avian influenza antigens. Today, three vaccines are approved in the United States for H5N1 influenza viruses though continued focus on surveillance and pandemic preparedness is essential to prepare for the possibility of human-to-human spread of this highly pathogenic influenza virus.

Fig. 1.

Phylogenetic evolution of the H5N1 influenza virus hemagglutinin. This figure identifies the phylogenetic evolution of the hemagglutinin proteins from H5N1 influenza virus isolates collected across the world between 1995 and 2024. Clade 2.3.4.4b arose in 2021 in Europe and the Americas (1).

Fig. 2.

Distribution of cell surface receptors where a sialic acid molecule is attached to a sugar chain via an a2,3 or a2,6 glycosidic linkage. Avian and human influenza species have different preferences for sialic acid linkages with avian influenza species typically binding strongly to a2,3 linked sialic acids and human influenza viruses usually preferring a2,6 linkages (dark gray). Recent human infections in dairy workers frequently have been associated with conjunctivitis with the human conjunctivae demonstrating cell receptors with a2,3 sialic acid linkage.

Fig. 3.

The addition of the adjuvant MF59 (triangles) demonstrates improved hemagglutinin inhibition antibody titers compared to unadjuvanted influenza virus hemagglutinin protein (squares). 3.75 mg of hemagglutinin protein mixed with MF59 demonstrated comparable immunogenicity to 90 mg of unadjuvanted hemagglutinin protein (15).

Fig. 4.

H5N1 vaccine mixed with MF59 produced cross-reactive antibody responses against four heterologous H5N1 viruses (18).

Fig. 5.

Hemagglutination inhibition antibody titers to Clade 2.3.4.4b hemagglutinin antigen from individuals vaccinated with H5 hemagglutinin antigens from Clade 1 virus (H5N1 A/Vietnam) with or without MF59 (panel e) or H5 hemagglutinin antigens from Clade 2.1 virus (H5N1 A/Indonesia) with or without AS03 (panel f) (21).