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

Abstract

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.

Keywords: DTaP-IPV-Hib vaccine; IgG response; Pneumococcal conjugate vaccine; Reactogenicity; Sex-differences; Vaccine effectiveness.