About: Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant.   Goto Sponge  NotDistinct  Permalink

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  • Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant.
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  • Virology
  • Immunology
  • Orthomyxoviridae
  • Immunostimulants
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