SANTA FE, N.M. – A single dose of an inactivated 2009 H1N1 influenza vaccine administered to pregnant women that contained 25 mcg of hemagglutinin antigen generated an antibody response typically associated with protection against influenza, results from a multicenter comparative trial showed.
Dr. Geeta K. Swamy
“It was anticipated and subsequently proven that a single dose of vaccine would be adequately immunogenic in the nonpregnant adult population,” Dr. Geeta K. Swamy reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “But there were questions raised as to what the appropriate dose should be during pregnancy, because there are issues with development of tolerance to foreign antigens during pregnancy. There is also a decrease in total circulating immunoglobulin levels during pregnancy, and there are concerns that this might have some modulation of effect on immune response to vaccines.”
In what she said is the first study of its kind, Dr. Swamy of Duke University Medical Center, Durham, N.C., and her associates at five other sites enrolled 120 women during their second or third trimester of pregnancy between Sept. 9, 2009, and Oct. 16, 2009. The women were randomized to receive either 25 mcg or 49 mcg of hemagglutinin antigen in a two-dose series separated by 21 days. The researchers used standard methods to test for hemagglutinin inhibition (HAI) in serum samples obtained before each vaccination and 21 days after the second vaccination.
The median age of study participants was 32 years, and most were white (85% of those in the 25-mcg group and 80% of those in the 49-mcg group). The sites included Duke; Group Health Research Institute, Seattle (lead site); Baylor College of Medicine, Houston; St. Louis (Mo.) University; Vanderbilt University, Nashville, Tenn.; and the University of Maryland, Baltimore.
Dr. Swamy reported that after the first vaccination, HAI titers of 1:40 or greater were detected in 93% of women in the 25-mcg group and 97% of women in the 49-mcg group, while the rate of seroconversion (defined as a fourfold increase in HAI titer from baseline) was 89% in the 25-mcg group and 97% in the 49-mcg group.
The geometric mean titers peaked after the first vaccination and did not increase further after the second vaccination. The vaccine was well tolerated, with mild-to-moderate transient side effects including tenderness at the injection site, malaise, and headache. “There was not any statistically significant difference between the 25-mcg dose and the 49-mcg dose, although the women in the higher-dose group did report more local tenderness and pain at the vaccine injection site,” Dr. Swamy said.
A stratified analysis of study participants who reported prior receipt of seasonal influenza vaccine showed trends toward a decline in geometric mean titers after the second dose of hemagglutinin antibody.
Further analyses are planned, she said, including investigating the optimal timing of vaccine administration during pregnancy.
The study was sponsored by the National Institute of Allergy and Infectious Diseases’ Vaccine and Treatment Evaluation Units network. Sanofi Pasteur provided the vaccine used in the study, but the company had no role in the conduct of the study or in analysis of the data.
Dr. Swamy said that she had no relevant financial conflicts to disclose.
Geeta K. Swamy