Vaccine- and antigen-dependent type 1 and type 2 cytokine induction after primary vaccination of infants with whole-cell or acellular pertussis vaccines

Abstract

Cytokine profiles were examined 1 month after primary vaccination of infants with a whole-cell pertussis vaccine (wP) (Connaught) or either of two acellular pertussis vaccines, aP-Chiron Biocine (aP-CB) or aP-SmithKline Beecham (aP-SB), each combined with diphtheria-tetanus toxoids (DT), in Bordetella pertussis antigen-stimulated or unstimulated peripheral blood mononuclear cells (PBMC). Pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were used as antigens, and the children were defined as responsive when their PBMC proliferated in response to these antigens. The controls were either children who received only DT or children who received pertussis vaccine but whose PBMC did not proliferate upon stimulation with B. pertussis antigens (unresponsive children). Antigen-stimulated PBMC of responsive wP recipients were characterized by an elevated production of T-helper-cell type 1 cytokines gamma interferon (IFN-␥) and interleukin 2 (IL-2), low to minimal production of IL-5, and no production of IL-4. The PBMC of aP vaccine-responsive recipients showed, in addition to the elevated IFN-␥ production, a consistent, antigendependent production of type 2 cytokines (IL-4 and IL-5), with PRN being the most and PT being the least effective antigen. Type 2 cytokine induction was more pronounced in aP-SB than in aP-CB recipients, as shown by the presence of IL-4 mRNA transcripts and higher IL-5 production in the former (161.6 ؎ 36 and 47.9 ؎ 44 pg/ml [mean ؎ standard error for five subjects each], respectively, after PRN stimulation). Appreciable, antigen-unstimulated (constitutive) IFN-␥ production was also detected in PBMC cultures of all vaccinees. However, this spontaneous IFN-␥ production was, in most vaccinees, significantly lower than the antigendriven cytokine production. In contrast, no constitutive type 2 cytokine production was ever observed in any vaccine group. PBMC from the two control groups (either DT or pertussis vaccine recipients) did not show any type 2 cytokine production, while IFN-␥ production was comparable in both antigen-stimulated and unstimulated conditions. Absence of type 2 cytokines and low levels of constitutive IFN-␥ production were also seen in prevaccination children. Thus, pertussis vaccines induce in infants a basically type 1 cytokine profile, which is, however, accompanied by some production of type 2 cytokines. The latter are more expressed by aP-SB than by aP-CB recipients, and with PRN than with other antigens, and they are minimally expressed in wP recipients and with PT as antigen. Our data also highlight a constitutive IFN-␥ production in infancy, which might reflect natural immunization and/or the burden of concomitant vaccinations and which may have an impact on T-helper-cell cytokine pattern polarization consequent to pertussis vaccination.

Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens

“…Consistent with the responses observed in mice, recovery from whooping cough in infants is associated with selective induction of Th1 cells. Immunization with Pw also induces Th1 cells, but Pa generate T cells with a mixed Th1/Th2 cytokine profile in children [6,7]. The findings of the present study demonstrate that this pattern of T cell cytokine production persists in a proportion of children for at least 4 years.…”

Longitudinal study of intracellular T cell cytokine production in infants compared to adults

“…The vaccines administered at 2, 4 and 6 months were against H. influenzae b, diphtheria, tetanus, B. pertussis and oral poliovirus. Although little information is available on vaccineinduced T cell cytokine responses in human infants, recent reports indicate pertussis vaccination induces predominately Th1 responses [23,24], while tetanus induces mixed Th1 and Th2 responses [25]. In the current study, it is difficult to distinguish between the influence of vaccination versus challenge by environmental antigens on cytokine positive T cell levels.…”

Passive Acquisition of Protective Antibodies Reactive with Bordetella pertussis in Newborns via Placental Transfer and Breast‐feeding

“…neutrophils as well as macrophages to eliminate intracellular bacteria. DTPa vaccines, on the other hand, promote a Th2 pattern, with production of several cytokines that activate B cells to produce neutralizing antibodies to inhibit bacterial adherence [39].…”