VACCINE-DEPENDENT AND ANTIGEN-DEPENDENT TYPE-1 AND TYPE-2 CYTOKINE INDUCTION AFTER PRIMARY VACCINATION OF INFANTS WITH WHOLE-CELL OR ACELLULAR PERTUSSIS VACCINES

Cytokine profiles were examined 1 month after primary vaccination of i nfants with a whole-cell pertussis vaccine (wP) (Connaught) or either of two acellular pertussis vaccines, aP-Chirou Biocine (aP-CB) or aP-S mithKline Beecham (aP-SB), each combined with diphtheria-tetanus toxoi ds (DT), in Bordetella pertussis antigen-stimulated or unstimulated pe ripheral blood mononuclear cells (PBMC), Pertussis toxin (PT), filamen tous hemagglutinin (FHA), and pertactin (PRN) were used as antigens, a nd the children were defined as responsive when their PBMC proliferate d in response to these antigens, The controls were either children who received only DT or children who received pertussis vaccine but whose PRMC did nest proliferate upon stimulation with B. pertussis antigens (unresponsive children), Antigen-stimulated PBMC of responsive wP rec ipients were characterized by an elevated production of T-helper-cell type I, cytokines gamma interferon (IFN-gamma) and interleukin 2 (IL-2 ), low to minimal production of IL-5, and no production of IL-4. The P BMC of aP vaccine-responsive recipients showed, in addition to the ele vated IFN-gamma production, a consistent, antigen-dependent production of type 2 cytokines (IL-4 and IL-5), with PRN being the most and PT b eing the least effective antigen. Type 2 cytokine induction was more p ronounced 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 subj ects each], respectively, after PRN stimulation), Appreciable, antigen -unstimulated (constitutive) IFN-gamma production was also detected in PBMC cultures of all vaccinees, However, this spontaneous IFN-gamma p roduction was, in most vaccinees, significantly lower than the antigen -driven cytokine production, In contrast, no constitutive type 2 cytok ine production was ever observed in any vaccine group, PBMC from the t wo control groups (either DT or pertussis vaccine recipients) did not show any type 2 cytokine production, while IFN-gamma production was co mparable in both antigen-stimulated and unstimulated conditions, Absen ce of type 2 cytokines and low levels of constitutive IFN-gamma produc tion were also seen in prevaccination children, Thus, pertussis vaccin es induce in infants a basically type 1 cytokine profile, which ist ho wever, accompanied by some production of type 2 cytokines, The latter are more expressed by aP-SB than by aP-CB recipients, and with PRN tha n with other antigens, and they are minimally expressed in wP recipien ts and with PT as antigen. Our data also highlight a constitutive IFN- gamma production in infancy, which might reflect natural immunization and/or the burden of concomitant vaccinations and which may have an im pact on T-helper-cell cytokine pattern polarization consequent to pert ussis vaccination.