The Qβ bacteriophage nanoparticle contributes to the adjuvanticity of antiglycan vaccines through a unique inflammatory pathway.

Abstract

Current glycoconjugate vaccines often fail to induce durable B cell memory or to provide sufficiently high-affinity antibodies limiting their utility for prophylactic protection against most bacterial and fungal pathogens. We address this limitation by engineering a chemically functionalized protein nanoparticle vaccine capable of eliciting protective nanomolar affinity antiglycan antibodies and long-term humoral memory. This platform incorporates a combination of two B cell-focused adjuvants, a TLR7 agonist and a natural killer T cell agonist, in order to enhance the antiglycan antibody maturation and memory formation. To define the contributions of each pathway, the antiglycan responses were evaluated at early and late time points following immunization. Although mice deficient in both TLR7 and natural killer T cell signaling revealed diminished primary immunization responses, an unexpectedly robust antiglycan antibody titer still developed and persisted for at least 1 yr after a two-dose immunization. These results indicate that durable antiglycan humoral immunity can develop independent of the chosen adjuvant pathways and may be driven by intrinsic adjuvanticity of the recombinant bacteriophage nanoparticle. Mechanistically, this effect was associated with an inflammatory response in which IFNγ and IL-1α appeared to play important roles. Together, these findings identify a previously unappreciated component contributing to long-term antiglycan immunity and support the use of bacteriophage-derived nanoparticles as platforms for vaccines against emerging antibiotic-resistant microorganisms.