Addressing this threat requires the development of effective vaccines and therapeutics specifically targeting evolving H5N1 viruses.
In the United States, several H5N1 vaccines, also known as Avian Influenza vaccines, have been developed from earlier HPAI H5N1 strains (A/Vietnam, clade 1, and A/Indonesia, clade 2.1). These vaccines have been licensed and stockpiled for pre-pandemic preparedness. Although, their effectiveness in generating neutralizing antibodies against the currently circulating H5N1 clade 2344b viruses has not been thoroughly assessed.
The study assessed the effectiveness of the AS03 adjuvanted A/Indonesia and the MF59 adjuvanted A/Vietnam vaccines, they were originally developed from earlier HPAI H5N1 strains. Despite their initial focus on different strains, they have shown the ability to produce neutralizing antibodies against the current clade 2344b strains.
In a conversation with Contagion, the FDA’s Center for Biologics Evaluation and Research (CBER) discussed the findings showed that individuals who received the AS03-adjuvanted A/Indonesia and MF59-adjuvanted A/Vietnam vaccines developed both cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2344b A/Astrakhan/3212/2020 virus. According to CBER, “The observed HAI geometric mean titers (GMT) and seroconversion rates (SCR) against the circulating H5N1 clade 2344b are significantly lower than the GMT and SCR observed against the strains in the FDA approved vaccines (A/Vietnam, clade 1 and A/Indonesia, clade 2.1),” a spokesperson said.
CBER continued to explain the approach known as immunobridging. “Immunobridging is a well-established approach to facilitate periodic updates to approved viral vaccines to better antigenically match rapidly evolving circulating viruses. Seasonal influenza vaccines provide an example of how bridging is used to make periodic updates to approved influenza vaccines. For each influenza season, a manufacturer’s approved seasonal influenza vaccine is used as a bridge to update their seasonal influenza vaccine to antigenically match the influenza viruses that are expected to circulate during the upcoming influenza season.”
Notably, seroconversion rates ranging from 60% to 95% against H5N1 clade 2344b were observed after administering either two doses of the AS03-adjuvanted A/Indonesia vaccine or three doses of the MF59-adjuvanted A/Vietnam vaccine. These results demonstrate that the adjuvanted vaccines are effective in eliciting an immune response against the currently circulating strains.
“This study shows that stockpiled H5N1 vaccines can generate cross-reactive binding antibodies to the H5N1 clade 2344b currently circulating in cow herds. These data may provide supportive evidence to bridge to updated H5N1 vaccines that antigenically match the circulating H5N1 clade 2344b virus(es),” CBER said.
This study evaluated the immunological responses to three licensed H5N1 vaccines in adults, including two adjuvanted versions—AS03-adjuvanted A/Indonesia and MF59-adjuvanted A/Vietnam—and one nonadjuvanted version. The assessment focused on key aspects such as antibody binding to the H5N1 clade 2344b virus, hemagglutination inhibition (to gauge the antibodies' ability to prevent virus-induced clumping of red blood cells), and the neutralizing antibody response (to determine how effectively the antibodies neutralize the virus and prevent infection).
CBER discusses the limitations and potential risks of using the existing adjuvanted H5N1 vaccines as a temporary measure until updated vaccines become available, “It is unknown whether the currently FDA-approved H5N1 vaccines in the national stockpile would protect humans against the currently circulating H5N1 clade 2344b strain(s). Further investigation is needed.”
The results demonstrate that current vaccines are effective for pre-pandemic preparedness and stress the need for ongoing monitoring and vaccine development to tackle evolving influenza threats. CBER also noted that clinical studies are ongoing to assess vaccines for the H5N1 clade 2344b strain. Therefore, while effective, further research is needed to confirm their protection and guide future vaccine updates.
