Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge

PLoS One. 2014 Aug 20;9(8):e104824. doi: 10.1371/journal.pone.0104824. eCollection 2014.

Abstract

There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-γ and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Female
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Vaccination / methods

Substances

  • Influenza Vaccines

Grants and funding

This work at the HZI was supported in part by grants from the EU (PANFLUVAC, TRANSVAC); BMBF in the context of the programs Gerontosys 2 (Gerontoshield), EuroNanoMed (HCVAX) and ERANetRUS (HCRUS). Maria Victoria Sanchez had a fellowship from CONICET and was in part supported by a fellowship from the German Academic Exchange Service (DAAD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.