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

Abstract

BackgroundPregnant 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.MethodsThe 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.Results58 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).ConclusionOur 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 RegistrationClinicalTrials.gov NCT01012557.

A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection

“…By contrast, vaccines against pandemic viruses such as H5N1 are typically poorly immunogenic and require multiple immunizations with high antigen doses and/or addition of adjuvants to achieve seroprotection [2]. This poor immunogenicity is compounded by pregnancy being a state of relative immune suppression, such that immunization during pregnancy may be less effective [3]. Inactivated seasonal influenza vaccines provide only 30–80% protection in healthy non-pregnant subjects [2] with vaccine effectiveness in pregnant women estimated to range from no protection up to 70% protection [4].…”

Immunological implications of pregnancy-induced microchimerism

“…For example, the severity of autoimmune disorders that affect non-reproductive tissues, such as rheumatoid arthritis and multiple sclerosis, markedly improves for women during pregnancy 15,16 . Similarly, the serological response to inactivated influenza vaccine is blunted during human pregnancy 17,18 . These systemic shifts in immune reactivity that occur during pregnancy probably extend to maternal immune components with specificity for fetal-expressed antigens given the FMC that results from widespread seeding and retention of genetically foreign fetal cells in the peripheral tissues of mothers (Fig.…”

Influenza immunization during pregnancy: Benefits for mother and infant

“…[22][23][24] This was also seen in pregnant women receiving MF59-adjuvanted pandemic vaccine (Focetria Ò ). 25,26 Pandemrix Ò , an AS03-adjuvanted pandemic vaccine, was similarly shown to be immunogenic in pregnant women in the UK. 24 Overall, 2009 H1N1 pandemic vaccine achieved high seroprotection rates of around 90% when given to pregnant women, regardless of the stage of gestation.…”

“…[42][43][44][45] A randomized controlled clinical trial comparing MF59-adjuvanted vaccine (Focetria Ò ) in pregnant and non-pregnant women found that a non-significant trend to a lower antibody response in pregnant women; 72% of the women reported adverse reactions, with 64% experiencing local reactions and 26% systemic reactions with malaise as the most common symptom. 25 …”