Multiparametric analysis of vaccine-induced B and T cell responses for optimal evaluation of memory immune responses to Bordetella pertussis in children

Abstract

Pertussis remains a serious health problem despite high global vaccination coverage. The identification of the optimal combination of blood immune markers to determine the persistence of specific memory responses to pertussis vaccines is needed to determine the optimal schedule of booster dose administrations. We evaluated different parameters of specific cellular immune responses in addition to antibody levels in three different cohorts of children considered to be still protected against whooping cough at the time of analysis. Group I (n = 13) received a whole-cell vaccine in infancy and two acellular vaccine (aPV) boosters. Group II (n = 31) had an aPV (Tetravac) in infancy and two aPV boosters. Group III (n = 42) received aPV (Infanrix-hexa) in infancy and one aPV booster. IgG against pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), tetanus and diphtheria toxins were measured by a fluorescent bead-based multiplex immunoassay, and the numbers of PT-, FHA-, PRN-specific memory IgG⁺ B cells (Bm) were enumerated by Elispot. PT-, FHA- and PRN-specific IFN-γ- and/or TNF-α-containing CD4⁺ T lymphocytes were enumerated by flow cytometry, as were the numbers of PT-, FHA-, and PRN-induced proliferating cells. Most children had detectable specific memory responses, but the patterns were very heterogenous. Th1-type CD4⁺ T cells and anti-FHA IgG and/or Bm responses characterized group I, whereas FHA- and PT-specific IgG and/or Bm responses were a hallmark of group II. Finally, Th1-type CD4⁺ T cells and FHA- and PRN-specific humoral and/or Bm responses were detected in group III. A combination of humoral and cellular markers of immunity to B. pertussis thus offers a more comprehensive assessment of immunity compared to serology alone and reveals that almost all recipients of a recent aP booster have several markers of immune memory.

Keywords: Antibodies; Bordetella pertussis vaccine; Filamentous haemagglutinin; Memory B cells; Memory T cells; Pertactin; Pertussis toxin.