Partial correction of the TH2/TH1 imbalance in neonatal murine responses to vaccine antigens through selective adjuvant effects

Abstract

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.

Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines

“…The peptide TT-P30 (FNNFTVSFWLRVPKVSASHLE), an immunodominant epitope of tetanus toxin (947-967), was synthesized commercially and used at the experimentally defined dose of 100 ? g [46]. TT and TT-P30 were adsorbed to Al(OH) 3 …”

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

“…Cairo and colleagues (24) have shown that IL-12 and IL-15 are expressed at lower levels in human cord blood, and this reduction in cytokine expression was speculated to contribute to the impairment of neonatal cell-mediated immunity. In addition, Barrios et al (9,10) demonstrated that neonatally immunized animals secrete higher levels of IL-5 and lower levels of IFN-␥ compared with adults. These findings have crucial implications for neonatal vaccine strategies that require robust Th1-type immune responses, particularly against viral diseases such as influenza, respiratory syncytial virus, and HIV.…”

“…Forsthuber et al (8) demonstrated that injection of neonatal animals with protein Ags in IFA actually induces immune deviation rather than tolerance and stimulates preferential expression of Th cell type 2 (Th2) cytokines and Ab isotypes. Similarly, Siegriest and colleagues (9,10) found that neonatal vaccine immunization results in biased Th2-type responses that still remain after adult boosting. Collectively, these findings have significant implications for neonatal vaccination strategies and suggest that redirection of the neonatal immune system to a Th1 pathway might increase responsiveness to vaccine Ags.…”

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

“…The IgG subclass pattern observed after early life immunization of mice is, nevertheless, characterized by a relatively high IgG1/IgG2a ratio [29,30]. This pattern reflects the Th2-biased conditions of the immune system in the newborn, shown by low production of IFN-c, but relatively high production of IL-4, IL-5 and IL-13 after immunization with TD antigens under neutral conditions [30][31][32][33].…”