Seasonal influenza vaccination for parturients is recommended because of their increased susceptibility to severe disease. The efficacy of inactivated influenza vaccine (IIV) in pregnant women may differ from that in healthy nonpregnant women or in men and could be more accentuated in parturients infected with HIV because of immunosuppression. This study comprised 2 blinded randomized controlled trials of trivalent IIV (IIV3) in parturients with and without HIV infection to evaluate safety, immunogenicity, and efficacy of IIV3 in these women and their infants to 24 weeks postpartum.
The women were aged 18 to 38 years, with estimated gestations of 20 to 36 weeks. The primary objectives for women without HIV infection were to evaluate the efficacy of IIV3 vaccination during pregnancy in protecting their infants against influenza through 24 weeks postpartum and to compare seroconversion rates between IIV3 recipients and placebo recipients 1 month after vaccination. In women with HIV, another objective was to evaluate the immunogenicity of IIV3 along with determining vaccine efficacy in mothers and their infants until 24 weeks postpartum. All mothers and infants in the HIV-infected cohort and a nested group of 180 HIV-uninfected mother-infant dyads were enrolled in a safety and immunogenicity study. Intention-to-treat and per-protocol analyses were conducted.
Among 2116 black African non–HIV-infected parturients, 1062 and 1054 received IIV3 and placebo, respectively; 1026 and 1023 live infants were born to IIV3 and placebo recipients, respectively. Of 194 HIV-infected parturients, 100 received IIV3 and 94 received placebo. Of the 376 participants in the immunogenicity subset, 142 IIV3 and 148 placebo recipients were included in the per-protocol analysis. Postvaccination geometric mean titers increased from baseline by a factor of 6 to 10 in IIV3 recipients and were significantly higher than titers in placebo recipients. A greater proportion of IIV3 recipients had seroprotective hemagglutination inhibition (HAI) titers after vaccination compared with placebo recipients. Newborns of IIV3 recipients had higher HAI geometric mean titers than newborns of placebo recipients and were more likely to have an HAI titer of 1:40 or greater. The newborn-to-maternal ratios of HAI titers were 0.7 to 1.0 and were similar between study groups. In the HIV-infected women in the per-protocol immunogenicity arm, receipt of IIV3 resulted in increases in geometric mean titers of antibodies. A higher proportion of IIV3 recipients had seroprotective HAI titers after vaccination compared with placebo recipients. Newborns of IIV3 recipients had higher HAI geometric mean titers than did newborns of placebo recipients. The ratio of geometric mean HAI titers was 0.7 to 1.4. In the IIV3 group, titers for HAI were higher than those in the placebo group. Attack rates for influenza among the IIV3 recipients was lower as compared with the placebo recipients, 1.8% versus 3.6%, respectively, indicating a vaccine efficacy of 50.4% (95% confidence interval [CI], 14.5%–71.2%). Similarly, the attack rate was 1.9% for infants whose mothers were IIV3 recipients compared with 3.6% for those whose mothers received placebo; vaccine efficacy was 48.8% (95% CI, 11.6%–70.4%). Vaccine efficacy estimates in the per-protocol analysis were similar to the estimates in the intention-to-treat analysis. In the HIV-infected mothers, the attack rate was 7.0% in IIV3 recipients compared with 17.0% for placebo recipients, for an adjusted vaccine efficacy of 57.7% (95% CI, 0.2%–82.1%). The attack rates were 5.0% and 6.8% among infants of IIV3 and placebo recipients, respectively (efficacy, 26.7%; P = 0.60). Injection-site reactions were more frequent among IIV3 recipients in both cohorts, but no other significant differences in reactions were found. No significant between-group differences were found for rates of miscarriage, stillbirth, or premature birth or birth weight in the HIV-uninfected or -infected cohort.
These results support the current World Health Organization recommendations for influenza vaccination during pregnancy, with a reduction in confirmed cases of influenza in both cohorts. Trivalent IIV was safe and immunogenic in HIV-uninfected and HIV-infected women. Because the study was conducted at a single center, the generalizability of the findings must be corroborated.