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.
Highlights
Seasonal vaccination against influenza is the best available measure to reduce the high impact of this pathogen on public health worldwide
The immunization with recombinant influenza nucleoprotein (rNP) co-administered with c-diAMP elicits strong antigen-specific humoral immune responses at systemic and mucosal levels
We evaluated the capacity of rNP adjuvanted with c-di-AMP to induce humoral and cellular immune responses when given by intranasal route
Summary
Seasonal vaccination against influenza is the best available measure to reduce the high impact of this pathogen on public health worldwide. The efficacy of current vaccines is mainly based on the induction of neutralizing antibodies that target the surface viral protein hemagglutinin (HA). This protein is subjected to a high degree of antigenic variation and new divergent strains continuously arise in nature, which are not recognized by antibodies induced by the vaccine. The vaccine seed stocks need to be updated every year [7] To overcome this limitation, efforts were invested in the development of a vaccine that can protect against the multiple antigenic variants, a concept that is known as ‘‘universal vaccine’’ [8]. This concept is based on the use of conserved antigens, such as the amino terminus of the M2 protein (M2e or M2 ectodomain) [9], the conserved stalk domain of the HA [10], the M1 protein and the nucleoprotein (NP) [11,12]
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