(625t) A Novel Vaccine for Streptococcus Pneumoniae Using Polyanhydride Nanoparticle Adjuvants

The World Health Organization estimates that pneumonia causes 1.6 million deaths every year, the majority in children in developing countries. Streptococcus pneumoniae is a leading cause of bacterial pneumonia in children. The current polysaccharide conjugate vaccine (PCV) has been shown to be effective in reducing cases of pneumonia, however it has several limitations. The vaccine is expensive and complicated to manufacture, leading to limited availability in developing countries, it does not provide cross-protection across pneumococcal serotypes, it has not been shown to prevent nasopharyngeal carriage, and the polysaccharide-based vaccine leads to poor immunogenicity in young children.

The pneumococcal surface protein PspA has demonstrated the ability to provide protection against challenge with S. pneumoniae, and has been found to be present on all known isolates of pneumonia, eliminating the need to include multiple serotypes in a vaccine. Additionally, the recombinant PspA protein is inexpensive to produce, which could lead to increased availability of a vaccine. It is also thought to play a role in nasopharyngeal carriage through its ability to bind to and prevent killing by apolactoferrin; therefore, vaccination with PspA could also provide protection against colonization. However PspA has not been proven to elicit an immune response without the addition of an adjuvant, and aluminum hydroxide, a commonly used adjuvant, requires a three-dose parenteral immunization regime to provide protection.

Polyanhydrides are a class of biomaterials that have shown much promise in drug and vaccine delivery because of their biocompatibility, controlled protein release kinetics, protein stabilization, and immune modulation. They can be fabricated into nanoparticles for administration via inhalation or injection and work effectively as vaccine adjuvants. Encapsulation of F1-V protein into nanoparticles made from copolymers of 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) recently demonstrated the ability to provide protection against intranasal challenge with Yersinia pestis. Furthermore, CPTEG:CPH nanoparticles degrade through a combination of bulk and surface erosion providing a sustained release of protein, while maintaining the protein’s structure and function. Encapsulation of the PspA antigen into the amphiphilic 50:50 CPTEG:CPH nanoparticles has demonstrated a sustained release of the protein over 60 days, and the released protein retained its primary structure as indicated by SDS-PAGE. Upon vaccination with the PspA-loaded (1μg/dose) 50:50 CPETG:CPH nanoparticles plus 2μg soluble PspA, in a single dose, mice elicited a humoral immune response indicated by the production of PspA specific antibodies, which was only slightly lower than mice immunized with the 3 dose regimen positive control (1μg PspA adsorbed to alum). These results provide evidence supporting the capabilities of amphiphilic polyanhydride nanoparticle-based adjuvants for the prevention and treatment of infectious respiratory diseases.