Prasert K.Praphasiri P.Lerdsamran H.Nakphook S.Ditsungnoen D.Chawalchitiporn S.Sornwong K.Poopipatpol K.Wirachwong P.Narakorn P.Surichan S.Suthepakul N.Thangsupanimitchai N.Pittayawonganon C.Puthavathana P.Davis W.W.Mott J.A.Olsen S.J.Patumanond J.Mahidol University2023-12-152023-12-152023-01-01Vaccine (2023)0264410Xhttps://repository.li.mahidol.ac.th/handle/20.500.14594/91449Background: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. Methods: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18–64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. Results: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = −22.0–76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: −2.77, 6.25), 2.22 (−2.40, 6.84), and −0.57 (−5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) Conclusions: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.vaccine.2023.11.0502-s2.0-851786097831873251838042698