Co-delivery of adjuvant and subunit antigens via a nanoparticle platform induces tissue-associated and systemic adaptive immune responses

Abstract Vaccination is a critical countermeasure against infection for both biodefense and public health. As many pathogens are encountered at mucosal interfaces, a delivery system that induces robust mucosal immunity is paramount. Here, we investigate a nanolipoprotein particle (NLP) containing the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) as a novel vaccine platform using disparate model antigens. Co-administration of MPLA-NLPs with ovalbumin significantly enhances the expansion of OVA-specific T cells in mice in vivo after a single intranasal inoculation, indicating that MPLA-NLPs function as efficient adjuvants. To combine the adjuvant effects with antigen delivery, we engineered MPLA-NLPs to accommodate attachment of His-tagged proteins. Intranasal administration of MPLA-NLPs conjugated to Bacillus anthracis antigens induces specific T cell responses in lung-draining lymph nodes and significant antibody responses in serum and bronchoalveolar lavage. Experiments to assess the immunogenicity of multiple antigens in combination on a single particle and to compare between co-administered formulations are ongoing. These data further support a role for NLPs as a flexible vaccine platform that allows co-delivery of antigen and adjuvant to lung-associated immune tissues and promotes robust adaptive immune responses.