Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses
01/2023
Journal Article
Authors:
Neuzil, K. M.;
Anderson, E. J.;
Frenck, R. W.;
Frey, S. E.;
Walter, E. B.;
Rupp, R.;
Rotrosen, E. T.;
Rouphael, N. G.;
Brady, R. C.;
Graham, I.;
Schmader, K. E.;
Porterfield, L.;
Ortiz, J. R.;
Swamy, G. K.;
El Sahly, H. M.;
Jeevan, T.;
Sitaula, R.;
Wegel, A.;
Webby, R. J. ;
Bryant, C.;
Influenza, A. H. N. Virus Vaccine Group
Journal:
Clin Infect Dis
PMID:
36610728
URL:
https://www.ncbi.nlm.nih.gov/pubmed/36610728
Keywords:
adjuvants avian influenza immunogenicity influenza vaccine
Abstract:
BACKGROUND: Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. METHODS: We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 mug or 15 mug hemagglutinin (HA); two doses of 15 mug HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 mug or 15 mug HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 mug or 15 mug HA, or 15 mug HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. RESULTS: We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 mug AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 mug adjuvanted groups. CONCLUSIONS: Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases.
