Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial

• Published in: PLoS ONE 2022, Vol.17 (10), p.e0274943
• Main Authors: Vanni, Tazio, Thomé, Beatriz C, Sparrow, Erin, Friede, Ma, Fox, Christopher B, Beckmann, Anna Marie, Huynh, Chuong, Mondini, Gabriella, Silveira, Daniela H, Viscondi, Juliana Y. K, Braga, Patrícia Emilia, Silva, Anderson da, Salomão, Maria da Graça, Piorelli, Roberta O, Santos, Joane P, Gattás, Vera Lúcia, Lucchesi, Maria Beatriz B, Oliveira, Mayra M. M. de, Koike, Marcelo E, Kallas, Esper G, Campos, Lucia M. A, Coelho, Eduardo B, Siqueira, Marilda A. M, Garcia, Cristiana C, Miranda, Milene Dias, Paiva, Terezinha M, Timenetsky, Maria do Carmo S. T, Adami, Eduardo A, Akamatsu, Milena A, Ho, Paulo Lee, Precioso, Alexander R
• Format: Report
• Language: English
• Subjects: Antigens; Clinical trials; Complications and side effects; Evaluation; Health aspects; Influenza vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0274943

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15[mu]g H7N9, 1B) IB160 + 7.5[mu]g H7N9, 1C) IB160 + 3.75[mu]g H7N9, 2A) SE + 15[mu]g H7N9, 2B) SE + 7.5[mu]g H7N9, 2C) SE + 3.75[mu]g H7N9, 3) unadjuvanted vaccine 15[mu]g H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers [greater than or equal to]40 in 45.2% of participants (MN titers [greater than or equal to]40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers [greater than or equal to]40 in 22.9% of participants (MN titers [greater than or equal to]40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.