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.

高致病性禽流感 (HPAI) H5N1 分支 2.3.4.4b 病毒在全球出现，及其向奶牛和动物（包括人类）的传播，对全球公共卫生构成重大威胁。因此，开发针对 H5N1 clade 2.3.4.4b 病毒的有效疫苗和治疗方法被认为是公共卫生优先事项。在美国，三种源自 HPAI H5N1 早期毒株（A/越南；进化枝 1 和 A/印度尼西亚；进化枝 2.1）病毒的三种 H5N1 疫苗已获得许可并储存，以备大流行前的准备。 ，但它们是否能够引发针对循环 H5N1 clade 2.3.4.4b 病毒的中和抗体尚不清楚。在这项研究中，我们评估了成人接种三种许可疫苗后产生的结合、血凝抑制和中和抗体反应。接种两种佐剂许可的 H5N1 疫苗的个体会产生针对 HPAI 进化枝 2.3.4.4b A/阿斯特拉罕/3212/2020 病毒的交叉反应结合和交叉中和抗体。在接种两剂 AS03 佐剂 A/印度尼西亚疫苗或三剂 MF59 佐剂 A/越南疫苗后，观察到针对 H5 进化枝 2.3.4.4b 的血清转化率为 60% 至 95%。这些发现表明，库存的美国许可的佐剂 H5N1 疫苗可产生针对人类循环 HPAI H5N1 分支 2.3.4.4b 的交叉中和抗体，并且在更新的 H5N1 疫苗问世之前可能可用作桥接疫苗。