Partial correction of the TH2/TH1 imbalance in neonatal murine responses to vaccine antigens through selective adjuvant effects.
We have recently shown that neonatal responses to a pannel of vaccine antigens and presentation systems differed qualitatively from adult responses by a bias towards a TH2 pattern. Here we report that a selected adjuvant comprising block copolymers in a water-in-oil emulsion can induce balanced TH1/TH2 responses in BALB/c mice primed at 1 week of age with an immunodominant tetanus peptide vaccine. However, using this specific TH1-driving adjuvant only at time of boosting was not sufficient to fully circumvent the persisting influence of TH2-biased neonatal responses. Unexpectedly also, a significant local toxicity was observed in newborn and young mice, whereas only mild reactions occurred in adults. Thus, although the induction of strong TH1 responses in the neonatal period can be achieved using specific adjuvants, through modulation of the immunological environment present at time of priming, whether such immunization strategies would be safe in the neonatal period remains to be demonstrated. These observations should be taken into consideration in the development of novel vaccines that will have to be already effective early in life.
Barrios
C
C
W.H.O. Collaborating Centre for Neonatal Vaccinology, University of Geneva, Switzerland.
Brandt
C
C
Berney
M
M
Lambert
P H
PH
Siegrist
C A
CA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011060:Poloxalene / Q000494:pharmacology*; D013744:Tetanus Toxin / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001428:Bacterial Vaccines; D016207:Cytokines; D015848:Interleukin-5; D013744:Tetanus Toxin; C086752:TiterMax; D015847:Interleukin-4; C041524:aluminum sulfate; D007371:Interferon-gamma; D011060:Poloxalene