Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus.

Abstract

Global emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses, and their transmission to dairy cattle and animals, including humans, pose a significant global public health threat. Therefore, development of effective vaccines and therapeutics against H5N1 clade 2.3.4.4b virus is considered a public health priority. In the U.S., three H5N1 vaccines derived from earlier strains of HPAI H5N1 (A/Vietnam; clade 1 and A/Indonesia; clade 2.1) virus, with (MF59 or AS03) or without adjuvants, are licensed and stockpiled for pre-pandemic preparedness, but whether they can elicit neutralizing antibodies against circulating H5N1 clade 2.3.4.4b viruses is unknown. In this study, we evaluated the binding, hemagglutination inhibition and neutralizing antibody response generated following vaccination of adults with the three licensed vaccines. Individuals vaccinated with the two adjuvanted licensed H5N1 vaccines generate cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates of 60% to 95% against H5 clade 2.3.4.4b were observed following two doses of AS03-adjuvanted-A/Indonesia or three doses of MF59-adjuvanted-A/Vietnam vaccine. These findings suggest that the stockpiled U.S. licensed adjuvanted H5N1 vaccines generate cross-neutralizing antibodies against circulating HPAI H5N1 clade 2.3.4.4b in humans and may be useful as bridging vaccines until updated H5N1 vaccines become available.