Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine

TLDR

The 2009 H1N1 pandemic was the first influenza pandemic of the 21st century. The study aimed to evaluate the immunogenicity and safety of a monovalent H1N1 vaccine with or without MF59 adjuvant in adults. Participants were randomized to receive two intramuscular injections of 7.5 µg hemagglutinin on day 0 and either day 7, 14, or 21, or two 3.75‑µg MF59‑adjuvanted doses, or 7.5 or 15 µg nonadjuvanted doses 21 days apart, with antibody responses measured by hemagglutination‑inhibition and microneutralization assays on days 0, 14, 21, and 42. MF59‑adjuvanted vaccine induced higher antibody titers and a greater proportion of subjects achieving protective levels by day 21 and day 42, with more frequent local reactions but only mild fever in three participants. ClinicalTrials.gov identifier NCT00943358.

Abstract

The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority.We conducted a single-center study, involving 176 adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms. Subjects were randomly assigned to receive two intramuscular injections of vaccine containing 7.5 microg of hemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21; or two 3.75-microg doses of MF59-adjuvanted vaccine, or 7.5 or 15 microg of nonadjuvanted vaccine, administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay and a microneutralization assay on days 0, 14, 21, and 42 after injection of the first dose.The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively; reactions were more common with the MF59-adjuvanted vaccine than with nonadjuvanted vaccine. Three subjects reported fever, with a temperature of 38 degrees C or higher, after either dose. Antibody titers, expressed as geometric means, were higher at day 21 among subjects who had received one dose of MF59-adjuvanted vaccine than among those who had received one dose of nonadjuvanted vaccine (P<0.001 by the microneutralization assay). By day 21, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 77 to 96% and 92 to 100% of subjects receiving MF59-adjuvanted vaccine, respectively, and in 63 to 72% and 67 to 76% of those receiving nonadjuvanted vaccine, respectively. By day 42, after two doses of vaccine, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 92 to 100% and 100% of recipients of MF59-adjuvanted vaccine, respectively, and in 74 to 79% and 78 to 83% of recipients of nonadjuvanted vaccine, respectively.Monovalent 2009 influenza A (H1N1) MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection after a single dose is administered. (ClinicalTrials.gov number, NCT00943358).