Use of biologic nanolipoprotein particles containing monophosphoryl lipid A as a novel intranasal vaccine platform for Bacillus anthracis

Abstract

Abstract There is considerable interest in developing a novel Bacillus anthracis vaccine that improves upon the shortcomings of the licensed vaccine for broader, more rapid protection of the population. Ideally, a vaccine would recognize the spore in addition to having anti-toxin effects as well as induce robust mucosal and lung-associated immunity for early recognition and clearance. Here, we investigate nanolipoprotein particles (NLPs) containing the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) as a platform for intranasal vaccination against Bacillus anthracis. Modified lipids enabled attachment of disparate spore and toxin protein antigens. Intranasal vaccination of mice with B. anthracis antigen-MPLA-NLP constructs vs. delivery with free MPLA induced robust IgG and IgA responses in serum and in bronchoalveolar and nasal lavage. Typically, a single dose sufficed to induce sustained antibody titers over time. Robust T cell responses to various spore antigens were also detected in the lung. When multiple immunizations were required, specific antibodies were detected earlier in the boost schedule with MPLA-NLP-mediated delivery than with free MPLA. Administering combinations of constructs induced robust responses to all incorporated antigens, indicating potential for a multivalent vaccine preparation. Experiments to determine the efficacy of multivalent vaccine preparations against inhalational B. anthracis challenge are ongoing. In summary, the NLP platform enhances humoral, cellular and mucosal responses to intranasal immunization, indicating promise for NLPs as a flexible, robust vaccine platform against B. anthracis and potentially other inhalational pathogens.