Michael I Hauser1, David J Muscatello2, Annabel C Y Soh1, Dominic E Dwyer3, Robin M Turner4. 1. University of New South Wales, Sydney, Australia. 2. School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia. Electronic address: david.muscatello@unsw.edu.au. 3. Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology - Institute of Clinical Pathology and Medical Research, Westmead Hospital and University of Sydney, Sydney, Australia. 4. Centre for Biostatistics, Division of Health Sciences, University of Otago, Dunedin, New Zealand. Electronic address: robin.turner@otago.ac.nz.
Abstract
BACKGROUND: Although oil-in-water adjuvants improve pandemic influenza vaccine efficacy, AS03 versus MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines are lacking. METHODS: We conducted an indirect-comparison meta-analysis extracting published data from randomised controlled trials in literature databases (01/01/2009-09/09/2018), evaluating immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. We conducted comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant versus unadjuvanted counterparts. Then via test of subgroup differences, we indirectly compared different AS03 versus MF59 regimens. RESULTS: We identified 22 publications with 10,734 participants. In adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR versus unadjuvanted vaccines (all four comparisons); MD = 0.56 (95%CI 0.33 to 0.80, p < 0.001) to 1.18 (95%CI 0.72 to 1.65, p < 0.001). MF59 (full-dose)-adjuvanted vaccines (7.5 µg haemagglutinin) were superior to unadjuvanted vaccines (three of four comparisons); MD = 0.47 (95%CI 0.19 to 0.75, p = 0.001) to 0.80 (95%CI 0.44 to 1.16, p < 0.001). Adult indirect comparisons favoured AS03 over MF59 (six of eight comparisons; p < 0.001 to p = 0.088). Paediatric indirect comparisons favoured MF59-adjuvanted vaccines (two of seven comparisons; p = 0.011, 0.079). However, unadjuvanted control group seroconversion rate was lower in MF59 than AS03 studies (p < 0.001 to p = 0.097). There was substantial heterogeneity, and adult AS03 studies had lower risk of bias. CONCLUSIONS: Despite limited studies, in adults, AS03-adjuvanted vaccines allow antigen sparing versus MF59-adjuvanted and unadjuvanted vaccines, with similar immunogenicity, but higher risk of pain and fatigue (secondary outcomes) than unadjuvanted vaccines. In children, adjuvanted vaccines are also superior, but the better adjuvant is uncertain.
BACKGROUND: Although oil-in-water adjuvants improve pandemic influenza vaccine efficacy, AS03 versus MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines are lacking. METHODS: We conducted an indirect-comparison meta-analysis extracting published data from randomised controlled trials in literature databases (01/01/2009-09/09/2018), evaluating immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. We conducted comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant versus unadjuvanted counterparts. Then via test of subgroup differences, we indirectly compared different AS03 versus MF59 regimens. RESULTS: We identified 22 publications with 10,734 participants. In adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR versus unadjuvanted vaccines (all four comparisons); MD = 0.56 (95%CI 0.33 to 0.80, p < 0.001) to 1.18 (95%CI 0.72 to 1.65, p < 0.001). MF59 (full-dose)-adjuvanted vaccines (7.5 µg haemagglutinin) were superior to unadjuvanted vaccines (three of four comparisons); MD = 0.47 (95%CI 0.19 to 0.75, p = 0.001) to 0.80 (95%CI 0.44 to 1.16, p < 0.001). Adult indirect comparisons favoured AS03 over MF59 (six of eight comparisons; p < 0.001 to p = 0.088). Paediatric indirect comparisons favoured MF59-adjuvanted vaccines (two of seven comparisons; p = 0.011, 0.079). However, unadjuvanted control group seroconversion rate was lower in MF59 than AS03 studies (p < 0.001 to p = 0.097). There was substantial heterogeneity, and adult AS03 studies had lower risk of bias. CONCLUSIONS: Despite limited studies, in adults, AS03-adjuvanted vaccines allow antigen sparing versus MF59-adjuvanted and unadjuvanted vaccines, with similar immunogenicity, but higher risk of pain and fatigue (secondary outcomes) than unadjuvanted vaccines. In children, adjuvanted vaccines are also superior, but the better adjuvant is uncertain.
Authors: Patricia Winokur; Hana M El Sahly; Mark J Mulligan; Sharon E Frey; Richard Rupp; Evan J Anderson; Kathryn M Edwards; David I Bernstein; Kenneth Schmader; Lisa A Jackson; Wilbur H Chen; Heather Hill; Abigail Bellamy Journal: Vaccine Date: 2021-01-21 Impact factor: 3.641
Authors: Joon Young Song; Won Suk Choi; Jung Yeon Heo; Jin Soo Lee; Dong Sik Jung; Shin-Woo Kim; Kyung-Hwa Park; Joong Sik Eom; Su Jin Jeong; Jacob Lee; Ki Tae Kwon; Hee Jung Choi; Jang Wook Sohn; Young Keun Kim; Ji Yun Noh; Woo Joo Kim; François Roman; Maria Angeles Ceregido; Francesca Solmi; Agathe Philippot; Alexandra C Walls; Lauren Carter; David Veesler; Neil P King; Hun Kim; Ji Hwa Ryu; Su Jeen Lee; Yong Wook Park; Ho Keun Park; Hee Jin Cheong Journal: EClinicalMedicine Date: 2022-07-22