Immunity to pertussis vaccination

Abstract

Thailand has implemented universal whole cell pertussis vaccination in children for more than 35 years; nevertheless, the numbers of reported pertussis cases are still on the rise, especially among infants below one year who bear the greatest risk of severe complications. Several countries have implemented a pertussis booster during adolescence. However, data on the appropriate age groups targeted for a booster in the Thai population is limited. The increase in pertussis incidence among Thai infants warrants the need to further investigate the pre-existing maternal antibody against Bordetella pertussis (B. pertussis) antigens and the potential benefit of Tetanus toxoid-reduced dose of diphtheria and acellular pertussis (Tdap) vaccine administered during pregnancy.

This study aims to investigate IgG antibody to pertussis toxin (anti-PT) among healthy people across all ages after 37 years of universal whole cell pertussis vaccination in Thailand and provide evidence-based recommendation for the age groups that should be targeted for a booster dose. This study also examined the baseline anti-PT, IgG antibody to filamentous hemagglutinin (anti-FHA) and IgG antibody to pertactin (anti-PRN) in Thai pregnant women who did not receive pertussis vaccine during pregnancy. The results showed that the antibody levels to all three B. pertussis antigens studied were low, which could result in susceptibility of Thai infants to pertussis. Then, this study evaluated and compared the antibody titers and T cell-mediated immune response induced by currently available acellular (aP) and whole cell (wP)-containing vaccine in infants born to mothers who received Tdap during pregnancy. The results revealed that in the presence of circulating B. pertussis-specific maternal antibodies induced by Tdap vaccination, infants who received aP had significantly higher levels of antibodies against all three B. pertussis antigens following primary immunization compared to infants who had received wP. However, at one month post booster dose, anti-PT level was similar but anti-FHA and anti-PRN were still higher in the aP group.

This study demonstrated the interference of maternal antibodies with the infant immune responses to wP, as shown by significantly higher antibody levels in the EPI wP group (no maternal immunization) compared to the wP group (with maternal immunization) for all three antigens studied following primary immunization. However, at one month post booster dose, we found that the blunting effect persisted for anti-PT and anti-FHA but not for anti-PRN. The clinical significance of these blunting effects is still unknown. However, monitoring the immunity of this cohort of children should be done in order to understand the long term impact of these immunological findings.

Regarding the T cell-mediated immune response, aP-vaccinated infants had higher Th1 cytokine responses at pre and post pertussis booster than wP-vaccinated children. For Th17 response following primary vaccination, the wP-vaccinated infants appeared to prime a better Th17 response than aP-vaccinated infants. Unlike the rapid waning of humoral immune response found at pre-booster, T cell-mediated immune response to pertussis toxin was still detectable and similar among all groups.

Maternal Tdap immunization can potentially reduce the antibody responses in infants vaccinated with the whole cell pertussis vaccine. Long-term monitoring of pertussis vaccine-induced immunity coupled with improved disease surveillance is warranted especially in countries using whole cell pertussis vaccines in their infant immunization program. However, cellular immune responses after the primary immunization and first booster did not appear to be significantly affected by maternal Tdap vaccination.