Influenza Vaccination of Pregnant Women and Protection of Their Infants

Madhi SA, Cutland CL, Kuwanda L. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371:918–31. Pregnant women are at risk for severe influenza from the second trimester to the early postpartum period, making them a priority group for seasonal influenza vaccination. Because pregnancy is characterized by the attenuation of cell-mediated immune responses, the efficacy of the inactivated influenza vaccine (IIV) in pregnant women may differ from that in nonpregnant women. Nevertheless, to date, no controlled trials have been performed to evaluate the efficacy of IIV during pregnancy. Furthermore, the vaccination of pregnant women may also confer partial protection against confirmed influenza in their infants. However, observational studies have had conflicting results with regard to the efficacy of the trivalent IIV during pregnancy in protecting infants against respiratory illness. The aim of this study was to evaluate the immunogenicity, safety, and efficacy of IIV in pregnant women and their infants until 24 weeks after birth. The authors performed 2 randomized, double-blind, placebo-controlled trials of trivalent IIV in pregnant women with and without human immunodeficiency virus (HIV). Healthy women aged 18 to 38 years with an estimated gestational age of 20 to 36 weeks were enrolled at 1 of 4 antenatal clinics in South Africa during the 2011 and 2012 influenza seasons. HIV-infected women who met these same eligibility criteria were enrolled during 2011. Participants were randomly assigned in a 1:1 ratio to receive IIV or placebo. Active surveillance for influenzalike illness was conducted through weekly contact with the participants. Women and infants identified as having influenza-like illness were tested for influenza virus by means of a reverse transcriptase–polymerase chain reaction (RT-PCR) assay. All the mothers and infants in the HIV-infected cohort and a nested group of uninfected mother–infant dyads were enrolled in an intensive safety and immunogenicity study. Those women were provided with diary cards on which to document for 1 week the possible local and systemic reactions to the vaccination, and blood samples were collected for hemagglutination inhibition (HAI) studies. A total of 2116 HIV-uninfected pregnant women were enrolled (mean age, 26.2 years; mean gestational age, 26.8 weeks) and gave birth to 2049 live infants. In the immunogenicity subset, seroconversion rates for strains A(H1N1), A(H3N2), and B(Victoria) among IIV recipients 1 month after immunization were 72.5%, 64.8%, and 92.3%, respectively; the rates among the placebo recipients were 8.1%, 2.7%, and 2.0%, respectively (P < .001 for all comparisons). Newborns of IIV recipients had higher HAI geometric mean titers for all the vaccine strains than did newborns of the placebo recipients, and they were also more likely to have an HAI titer of 1:40 or higher for A(H1N1) (81.1% vs 34.0%, respectively), A(H3N2) (60.0% vs 17.5%, respectively), and B (82.1% vs 43.7%, respectively) (P < .001 for all comparisons). The attack rate for RT-PCR–confirmed influenza among both the placebo recipients and their infants was 3.6%. The attack rates among IIV recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5–71.2) and 48.8% (95% CI, 11.6–70.4). A total of 194 HIV-infected women were included (mean maternal age, 28.2 years; mean gestational age, 27.3 weeks; baseline median CD4 T-cell count, 393.5 cells per μL; median level of plasma HIV-1 RNA, 1067 copies per milliliter). The attack rate for the placebo recipients was 17.0%, and the rate for IIV recipients was 7.0%; Literature Review