Single-Dose Vaccination for the 2009 H1N1 Influenza A Virus
By Amesh A. Adalja, MD, September 15, 2009
Vaccination strategy for the 2009 H1N1 influenza A pandemic has been premised on the assumption that 2 doses of vaccine will be needed to generate a sufficient antibody response to afford protection. However, 2 studies published ahead of print in the New England Journal of Medicine provide evidence that a single dose of vaccine may be sufficient.
CSL’s Unadjuvanted Vaccine Conferred Seroprotection in 96.7% of Subjects
The Australian company CSL Limited—a provider of U.S. seasonal flu vaccine—conducted a Phase II study involving 240 subjects aged 18 to 64 years. Subjects who were pregnant or who may have had prior exposure to the novel virus were excluded. Subjects were inoculated with either a 15- or a 30-microgram unadjuvanted, chicken-egg derived vaccine. A single dose of the vaccine produced sufficient titers (hemagglutinin-inhibition assay titers [HAI] of 1:40 or greater) in 96.7% of the subjects who received the 15-microgram version and in 93.3% who received the 30-microgram injection.1
No Serious Adverse Events
There were no serious adverse events reported in the study, and fewer than half of the subjects complained of local adverse events (eg, injection site tenderness) or systemic adverse events (eg, headache, malaise, etc).1
Immunological Phenomena Observed
Several interesting immunological phenomena were uncovered during the study:
31.7% of subjects had baseline antibody titers of 1:40 or more to the novel virus.
44.4% of those who had received the 2009 seasonal vaccine (Southern Hemisphere version) had titers of 1:40 or more to the novel virus, while only 21.2% of those that did not receive the seasonal vaccine had similar levels of titers.
Subjects over age 50 had less robust responses to the vaccine than did those in younger age cohorts.1
The Novartis MF59-Adjuvanted Vaccine Conferred Seroprotection in Up to 92% of Recipients
Another study published by the New England Journal Medicine revealed the results of an interim analysis of a study of 100 adults who received a 7.5-microgram dose of the Novartis novel vaccine. (Novartis is also a seasonal influenza manufacturer for the U.S.) The Novartis vaccine uses the MF59 adjuvant and is grown on cells (as opposed to chicken eggs). On day 21 after vaccination, 92% of those vaccinated had protective antibody titers as measured by HAI.2
As is expected with the use of immune-boosting adjuvants, 86% of the subjects who received the Novartis vaccine reported mild adverse events, with pain at the injection site being the most common event reported. No serious adverse events were reported.2
One-Dose Vaccination May Not Be a Panacea
The fact that a one-dose vaccination may prove to be feasible is a very important finding, because it has the potential to decrease the amount of resources needed for the pandemic vaccine campaign. But there are 2 major caveats to the findings:
- The peak of the influenza wave in the Northern Hemisphere is expected to occur earlier than usual (in the second half of October) and before substantial amounts of vaccine are available (it is anticipated that vaccine will be available in limited quantities by mid-October).3,4
- As pointed out in an accompanying editorial by Kathleen Neuzil in the New England Journal of Medicine, these studies were not conducted in high-risk groups, such as pregnant women, young children, and people who are immunosuppressed. The robust immune response seen in healthy adults may not be replicable in other cohorts.5
Overall, the findings do provide hope that even if we are not able to flatten the peak of disease activity, some proportion of the population may be able to stave off disease in the post-peak activity period.
Greenberg ME, Lai MH, Hartel GF, et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine—preliminary report. N Engl J Med 2009. http://content.nejm.org/cgi/content/full/NEJMoa0907413. Accessed September 13, 2009.
Clark TW, Pareek M, Hoschler K, et al. Trial of influenza A (H1N1) 2009 monovalent MF59-adjuvanted vaccine—preliminary report. N Engl J Med 2009. http://content.nejm.org/cgi/content/full/NEJMoa0907650. Accessed September 13, 2009.
CDC. Press Briefing Transcript. Media Briefing: Update on 2009 H1N1 Flu. September 3, 2009. http://www.cdc.gov/media/transcripts/2009/t090903.htm. Accessed September 13, 2009.
Balcan D, Hu H, Goncalves B, et al. Seasonal transmission potential and activity peaks of the new influenza A (H1N1): a Monte Carlo likelihood analysis based on human mobility. BMC Medicine 2009. http://www.biomedcentral.com/1741-7015/7/45/abstract. Accessed September 13, 2009.
Neuzil KM. Pandemic influenza vaccine policy—considering the early evidence. N Engl J Med 2009. http://content.nejm.org/cgi/content/full/NEJMe0908224. Accessed September 13, 2009.