Nanoparticles Containing Streptococcus pneumoniae Polysaccharide Drive A Protective B Cell Respons

Vaccines are most effective at preventing infectious disease in humans by eliciting a strong protective antibody response. When cluster of differentiation 4 positive T helper cells interacts with B cells, a humoral response is enabled and antigen specific antibodies are produced. To help bolster the immune response of a poorly immunogenic polysaccharide antigen, a B cell antigen can be conjugated to a T cell epitope. This type of vaccine approach has limitations that can be improved upon. It is very expensive to produce and cost can be a limiting factor for accessibility of vaccines in the developing world where people are most in need. It is also a very complex process to conjugate proteins, limiting the number of capsular serotypes that can be added to current vaccines and allowing for the emergence of non-vaccine serotypes. Lastly, protein conjugate vaccines rely heavily on cluster of differentiation 4 positive T cells that are restricted by the highly polymorphic major histocompatibility complex class II complex. The major histocompatibility complex molecule has thousands of different alleles among individuals meaning the level of a vaccine effectiveness will be dependent on a person's genotype. By harnessing help from a special subset of T cells called invariant natural killer T cells, we can help B cells while avoiding those limitations. Invariant natural killer T cells are a subset of innate-like T cells that recognize glycolipids presented by the non-polymorphic molecule, cluster of differentiation 1. To recruit this subset of cells we have created a nanoparticle loaded with alpha-Galactosylceramide, a potent activator of invariant natural killer T cells, and embedded it with polysaccharide B cell antigens. We found that activation of invariant natural killer T cells with the nanoparticle lead to B cell activation that produced a specific antibody response against Streptococcus pneumoniae polysaccharide serotype 3 that was then able to protect against infection. Once synthesis of this first set of particles was optimized, we made a new set of particles incorporating a second polysaccharide, Streptococcus pneumoniae polysaccharide serotype 1. This serotype is interesting because it is zwitterionic and has been shown to activate cluster of differentiation 4 positive T cells through the major histocompatibility complex class II which is generally thought of as peptide antigen specific. This nanoparticle with both serotypes was able to activate invariant natural killer T cells in vivo to produce interleukin 4 and interferon gamma. This success with a second serotype shows that multiple serotypes can be included in the same vaccine. Adjustments to the protocol for nanoparticle synthesis are needed before definitively showing that this combination can elicit a protective B cell response against Streptococcus pneumoniae of either serotype, but initial indications are promising.