Differences by sex in IgG levels following infant and childhood vaccinations: An individual participant data meta-analysis of vaccination studies

Background If immune responses to vaccination differ between males and females, sex-specific vaccination schedules may be indicated. We systematically reanalysed childhood vaccination studies conducted in The Netherlands for sex-differences in IgG-responses. To assess the impact of potential sex-differences in IgG-responses, we explored sex-differences in vaccine failure/effectiveness and reactogenicity. Methods Six studies with IgG-measurements for 1577 children following infant pneumococcal (PCV7/PCV10/PCV13) and/or DTaP-IPV-Hib(-HepB) vaccinations, or the pre-school DTaP-IPV booster were included. We performed one-stage individual participant data meta-analyses per time-point of the effect of sex on IgG levels against pneumococcal serotypes, diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP using linear mixed models. Using existing study data, we compared reactogenicity after PCV7/PCV10 and DTaP-IPV-Hib(-HepB) vaccination in girls and boys. Vaccine failure/effectiveness was compared between girls and boys for invasive pneumococcal disease (IPD), invasive Hib disease and pertussis using notification data. Results For pneumococcal vaccination, the geometric mean concentration ratio of IgG levels in girls versus boys pooled across serotypes was 1.15 (95%CI 0.91–1.45) 1 month following the primary series, 1.16 (1.02–1.32) at age 8 months, 1.12 (1.02–1.23) pre-booster (age 11 months) and 0.99 (0.89–1.10) post-booster (age 12 months). Diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP IgG levels did not differ between girls and boys, except for Hib post-booster (1.24; 95%CI 1.01–1.52) and tetanus before pre-school booster (0.71; 0.53–0.95). We found no difference between boys and girls in reactogenicity at age 4 or 11 months or in vaccine failure/effectiveness for IPD, invasive Hib disease or pertussis. Conclusion For most vaccine antigens investigated, there were no consistent differences in vaccine-induced IgG levels. Vaccine-induced pneumococcal IgG levels were slightly higher in girls, but only between the primary series and the 11-month booster. These results, along with similar reactogenicity and vaccine failure/effectiveness, support the uniform infant vaccination schedule in the Dutch national immunisation programme.