Background: Despite widespread use of whole-cell (wP) and acellular (aP) pertussis vaccines, outbreaks persist in many countries. Polymorphisms in HLA class II molecules, which present antigens to CD4+ T cells, may play a vital role in vaccine responses. Emerging evidence suggests that HLA-DR/DQ variants can significantly influence wP vaccine responses. This study investigated the possible association of HLA class II haplotypes with antibody concentrations after aP booster vaccination.

Materials and methods: Healthy Finnish children (7-10y, n = 37), adolescents (11-15y, n = 37), young adults (20-34y, n = 25), and older adults (60-70y, n = 25) received a Tdap3-IPV booster. Serum antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT), as well as PT-neutralizing antibodies (PTNA), were measured before, one month, and one year after the booster. Participants were HLA-typed with a stepwise HLA-DR/DQ screening system using PCR followed by allele-specific probe hybridization. The frequency of HLA haplotypes was compared to the control cohort from the Finnish Pediatric Diabetes Register, which was constructed from parental haplotypes not passed down to diabetic children.

Results: The HLA DR-DQ haplotype frequencies in our cohort did not differ from the control group. Two associations survived FDR correction: (DR7)-DQA1*02:01-DQB1*02 with lower anti-PT IgG and (DR15)-DQB1*06:02 with a time-dependent anti-FHA IgG response with higher pre-booster concentrations. Nominally, (DR8)-DQB1*04 and (DR7)-DQA1*02:01-DQB1*02 carriers had lower PTNA; (DR9)-DQA1*03-DQB1*03:03, (DR15)-DQB1*06:02, and DRB1*04:01-DQA1*03-DQB1*03:02 carriers had higher anti-PT and anti-Prn concentrations; and (DR13)-DQB1*06:03 carriers had consistently lower anti-DT across all timepoints.

Conclusions: The present study highlights a potential role of certain HLA haplotypes in modulating immune responses to aP vaccination. These findings emphasize the importance of further research to clarify how HLA class II haplotypes influence aP vaccine responses in various populations.