Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

摘要: ABSTRACT Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use infants less than 6 months of age, part due to the weak immune response following vaccination. Thus, there strong need develop new with improved efficacy this vulnerable population. To address issue, we established neonatal African green monkey (AGM) nonhuman primate model that could be used identify effective influenza vaccine approaches We assessed ability flagellin, Toll-like receptor 5 (TLR5) agonist, serve as an adjuvant at-risk Four- 6-day-old AGMs were primed boosted inactivated PR8 (IPR8) adjuvanted either wild-type flagellin or inactive mutation at position 229 (m229), latter which incapable signaling through TLR5. Increased IgG responses observed boost, well early times after challenge, vaccinated flagellin-adjuvanted IPR8. Inclusion during also resulted significantly increased number virus-specific T cells challenge compared m229 adjuvant. Finally, IPR8 plus exhibited reduced pathology lungs received m229. This study provides first evidence flagellin-mediated enhancement neonates. IMPORTANCE Young particularly susceptible severe disease result infection. Compounding lack Here describe approach results protection Incorporation antibody cell together These suggest may targeted