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 MF59H-adjuvanted vaccine (FocetriaH) in H1N1pnd09-naı̈ve 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 mg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 mg); (2) 3.75 mg antigen half MF59-adjuvanted (Pa3.75 mg); (3) 15 mg antigen unadjuvanted (P15 mg); and in non-pregnant women receiving (4) 7.5 mg antigen full adjuvanted (NPa7.5 mg). 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 mg and 149 non-pregnant women were recruited to NPa7.5 mg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 mg) compared with pregnant (Pa7.5 mg) 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 betwee