Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial

Background:Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.Methods:The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC₂₀₁₀) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1:1:1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 μg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 μg); (2) 3.75 μg antigen half MF59-adjuvanted (Pa3.75 μg); (3) 15 μg antigen unadjuvanted (P15 μg); and in non-pregnant women receiving (4) 7.5 μg antigen full adjuvanted (NPa7.5 μg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.Results:58 pregnant women were allocated to Pa7.5 μg and 149 non-pregnant women were recruited to NPa7.5 μg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 μg) compared with pregnant (Pa7.5 μg) women (OR = 2.48 [1.03-5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85-1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 μg) and non-pregnant (NPa7.5 μg) groups (OR = 0.49 [0.13-1.85], p = 0.29).Conclusion:Our study suggests the immune response to the 7.5 μg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.Trial Registration: ClinicalTrials.gov NCT01012557.