Delta inulin alone or combined with CpG oligonucleotide enhances antibody‐dependent influenza vaccine protection in mice and nonhuman primate newborns

Newborns represent over half of hospitalized pediatric influenza infection cases, with current influenza vaccines not effective in the first months of life. Advax^® (delta inulin) is a polysaccharide particle that targets DC-SIGN, whereas CpG55.2 is a potent murine and human toll-like receptor (TLR)-9 agonist. This study asked whether Advax or CpG alone, or combined, could enhance the protection of an inactivated influenza virus vaccine (IIV) in newborns. One-day-old mouse pups were immunized subcutaneously with a single dose of IIV alone or with Advax or Advax-CpG55.2 adjuvants and then, at 28 days of age, challenged intranasally with a lethal dose of influenza virus. While IIV alone or with CpG adjuvant provided minimal protection, Advax alone or combined with CpG55.2 induced enhanced serum anti-influenza IgM and IgG responses to IIV and protected the newborns against clinical disease. Protection induced by a single vaccine dose was highly durable and was still evident 6-9 months after a single neonatal immunization. Protection was lost in B-cell-deficient μMT pups but preserved in β2m knockout pups and in CD4⁺ and CD8⁺ T-cell-depleted pups, indicating the importance of intact humoral immunity to the enhanced protection. The neonatal benefits of Advax^® and Advax-CpG55.2 adjuvant were confirmed in newborn macaques, where they similarly enhanced serum anti-influenza antibody responses to IIV. This raises the possibility that Advax^® adjuvant alone or in combination with CpG55.2 may have utility in improving influenza vaccine protection in human newborns.