|N Engl J Med. 2009 Sep 10. |
Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine -- Preliminary Report.
Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, Basser RL.
From Clinical Research and Development, CSL, Parkville, VIC, Australia.
BACKGROUND: A novel influenza A (H1N1) 2009 virus is responsible for the first influenza pandemic in 41 years. A safe and effective vaccine is urgently needed. A randomized, observer-blind, parallel-group trial evaluating two doses of an inactivated, split-virus 2009 H1N1 vaccine in healthy adults between the ages of 18 and 64 years is ongoing at a single site in Australia. METHODS: This preliminary report evaluates the immunogenicity and safety of the vaccine 21 days after the first of two scheduled doses. A total of 240 subjects, equally divided into two age groups (<50 years and >/=50 years), were enrolled and underwent randomization to receive either 15 mug or 30 mug of hemagglutinin antigen by intramuscular injection. We measured antibody titers using hemagglutination-inhibition and microneutralization assays at baseline and 21 days after vaccination. The coprimary immunogenicity end points were the proportion of subjects with antibody titers of 1:40 or more on hemagglutination-inhibition assay, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in the geometric mean titer. RESULTS: By day 21 after vaccination, antibody titers of 1:40 or more were observed in 116 of 120 subjects (96.7%) who received the 15-mug dose and in 112 of 120 subjects (93.3%) who received the 30-mug dose. No deaths, serious adverse events, or adverse events of special interest were reported. Local discomfort (e.g., injection-site tenderness or pain) was reported by 46.3% of subjects, and systemic symptoms (e.g., headache) by 45.0% of subjects. Nearly all events were mild to moderate in intensity. CONCLUSIONS: A single 15-mug dose of 2009 H1N1 vaccine was immunogenic in adults, with mild-to-moderate vaccine-associated reactions. (ClinicalTrials.gov number, NCT00938639.) Copyright 2009 Massachusetts Medical Society.
PMID: 19745216 [PubMed - as supplied by publisher]
N Engl J Med. 2009 Sep 10.
Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine -- Preliminary Report.
Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, Groth N, Stephenson I.
From the Infectious Diseases Unit, University Hospitals Leicester and Department of Inflammation, Infection and Immunity, University of Leicester, Leicester, United Kingdom (T.W.C., M.P., H.D., K.G.N., I.S.); the Respiratory Virus Laboratory, Health Protection Agency, London (K.H.); and Novartis Vaccines and Diagnostics, Siena, Italy (N.G.). Drs. Clark and Pareek contributed equally to this article.
BACKGROUND: 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. METHODS: We conducted a single-center study, involving 175 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 mug 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-mug doses of MF59-adjuvanted vaccine, or 7.5 or 15 mug 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. RESULTS: Results of an interim analysis of the responses to the 7.5-mug dose of MF59-adjuvanted vaccine by days 14 and 21 are presented (data from four of the seven groups studied, for a total of 100 subjects). The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively. Two subjects reported fever, with a temperature of 38 degrees C or higher, after the first dosing. Antibody titers, expressed as geometric means, were generally higher at day 14 among subjects who had received two 7.5-mug doses of the MF59-adjuvanted vaccine than among those who had received only one by this time point (P=0.04 by the hemagglutination-inhibition assay and P<0.001 by the microneutralization assay). By 21 days after vaccination with the first dose of 7.5 mug of MF59-adjuvanted vaccine, the rates of seroconversion, as measured with the use of a hemagglutination-inhibition assay and a microneutralization assay, were 76% and 92% of subjects, respectively, who had received only one dose to date (with the second dose scheduled for day 21) and 88 to 92% and 92 to 96% of subjects, respectively, who had already received both doses (P=0.11 and P=0.64, respectively). CONCLUSIONS: In preliminary analyses, the monovalent influenza A (H1N1) 2009 MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection within 14 days after a single dose is administered. (ClinicalTrials.gov number, NCT00943358.)