September 11, 2009 — Two studies reported online September 10 in the New England Journal of Medicine suggest that monovalent 2009 influenza A (H1N1) vaccines appear to be immunogenic in adults, with mild to moderate vaccine-associated reactions.
"A novel influenza A (2009 H1N1) virus is responsible for the first influenza pandemic in 41 years," write Michael E. Greenberg, MD, MPH, from CSL, Parkville, Victoria, Australia, and colleagues. "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."
In this preliminary report, the investigators describe the immunogenicity and safety of the vaccine at 21 days after the first of 2 scheduled doses among 240 participants, who were equally divided into 2 age groups (<50>
At baseline and 21 days after vaccination, antibody titers were measured with hemagglutination-inhibition and microneutralization assays. Outcomes reflecting immunogenicity were the proportion of subjects with antibody titers of 1:40 or more on hemagglutination-inhibition assay, the proportion of participants with either seroconversion or a significant increase in antibody titer, and the factor increase in geometric mean titer.
Antibody titers of 1:40 or more by day 21 after vaccination were documented in 116 (96.7%) of 120 participants vaccinated with 15-μg hemagglutinin antigen and in 112 (93.3%) of 120 participants vaccinated with 30-μg.
First Study: Immunogenic and Mild Adverse Events
Nearly all adverse events were mild to moderate in intensity, including injection-site tenderness or pain in 46.3% of participants and systemic symptoms such as headache in 45.0% of participants. There were no reported deaths, serious adverse events, or adverse events of special interest.
"A single 15-mcg dose of 2009 H1N1 vaccine was immunogenic in adults, with mild to moderate vaccine-associated reactions," the study authors write. "Estimates of the true effect of the vaccine when used in mass immunization programs will come from vaccine-effectiveness studies."
Limitations of this study include its lack of generalizability to groups other than healthy adults or to other geographic locations.
The second study, by Tristan W. Clark, MRCP, from the University of Leicester, United Kingdom, and colleagues, was a single-center study designed to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine in both MF59-adjuvanted and nonadjuvanted forms. Age range of the participants (n = 175) was 18 to 50 years.
Participants were randomly assigned to receive 2 intramuscular injections of vaccine containing 7.5 μg of hemagglutinin on day 0 in each arm or 1 injection on day 0 and the other on day 7, 14, or 21; or two 3.75-μg doses of MF59-adjuvanted vaccine or 7.5- or 15-μg doses of nonadjuvanted vaccine, given 21 days apart. Hemagglutination-inhibition assay and a microneutralization assay on days 0,14, 21, and 42 after injection of the first dose allowed determination of antibody responses.
An interim analysis of the responses to the 7.5-μg dose of MF59-adjuvanted vaccine by days 14 and 21 used data from 100 participants in 4 of the 7 groups studied.
Pain at the injection site was the most frequent local reaction, occurring in 70% of the participants. The most frequent systemic reaction was muscle aches, occurring in 42% of the participants. Fever (temperature, 38°C or higher) occurred in 2 patients after the first dosing.
Second Study: Protection Likely After 14 Days
At day 14, antibody titers, expressed as geometric means, were generally higher in participants who had received two 7.5-μg doses of MF59-adjuvanted vaccine than in those who had received only 1 dose by this time (P = .04 by the hemagglutination-inhibition assay and P < .001 by the microneutralization assay).
Rates of seroconversion by 21 days after vaccination with the first dose of 7.5 μg of MF59-adjuvanted vaccine, as measured with hemagglutination-inhibition assay and microneutralization assay, were 76% and 92% of participants, respectively, who had received only 1 dose to date (with the second dose scheduled for day 21) and 88% to 92% and 92% to 96% of participants, respectively, who had already received both doses (P = .11 and P = .64, respectively).
"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," the study authors write.
Study limitations include lack of recognized immune correlates for immunogenicity data and the inability to rule out asymptomatic infection with H1N1.
In an accompanying editorial, Kathleen M. Neuzil, MD, MPH, from PATH, Seattle, Washington, notes that "the robustness and consistency of the antibody response, and the use of internationally standardized reagents and controls, are reassuring and lend credibility to the results of Greenberg et al. and Clark et al.
"In our current global situation, in which demand for influenza vaccine greatly exceeds supply, dose-sparing strategies are needed," Dr. Neuzil writes. "Fewer or partial doses and the use of adjuvants can all contribute to increased global vaccine supply. The studies by Greenberg et al. and Clark et al. provide evidence that such strategies may be successful for the current pandemic."
CSL supported the first study, with funding from the Department of Health and Aging of the Australian government, and employs all of its authors. The second study was supported by grants from University Hospitals Leicester and Novartis; some of the study authors have disclosed various financial relationships with Illumina, Novartis, GlaxoSmithKline, Baxter, Sanofi Pasteur, and/or Hoffmann-LaRoche. Dr. Neuzil has disclosed no relevant financial relationships.
N Engl J Med. Published online September 10, 2009.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου