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Immunol Cell Biol . Delta inulin alone or combined with CpG oligonucleotide enhances antibody-dependent influenza vaccine protection in mice and non

tetano

Editor, Senior Moderator
Immunol Cell Biol


. 2025 Jun 29.
doi: 10.1111/imcb.70045. Online ahead of print. Delta inulin alone or combined with CpG oligonucleotide enhances antibody-dependent influenza vaccine protection in mice and nonhuman primate newborns

Isaac G Sakala[SUP] 1 2 [/SUP], Yoshikazu Honda-Okubo[SUP] 1 2 [/SUP], Nikolai Petrovsky[SUP] 1 3 [/SUP]



Affiliations
Abstract

Newborns represent over half of hospitalized pediatric influenza infection cases, with current influenza vaccines not effective in the first months of life. Advax[SUP]®[/SUP] (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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T-cell-depleted pups, indicating the importance of intact humoral immunity to the enhanced protection. The neonatal benefits of Advax[SUP]®[/SUP] 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[SUP]®[/SUP] adjuvant alone or in combination with CpG55.2 may have utility in improving influenza vaccine protection in human newborns.

Keywords: adjuvant; immunity; infection; influenza; neonate; vaccine.

 
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