Capsular polysaccharides (CPS) are a major virulence factor in meningococcal infections and form the basis for serogroup designation and protective vaccines. Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis in young children and young adults with high mortality rate. The current polysaccharide meningococcal vaccines that are available are very expensive. These vaccines are Menactra™ (MCV4 is a quadrivalent conjugate vaccine) and Menomune® (MPSV4 is a quadrivalent polysaccharide vaccine), both containing serogroups A, C, W135 and Y. However, neither vaccine is licensed for use in children under 2 years of age, since they are poorly immunogenic in infants due to their under-developed immune responses. Therefore, the search for novel vaccine formulations that overcome the limitations of the current conjugate vaccines is important. The long-range goal of the proposed project is to investigate a novel oral meningococcal vaccine formulation with adjuvant that can induce protective immune responses utilizing nanoparticle technology.
The proposed vaccine formulation consists of meningococcal CPS polymers encapsulated in albumin-based nanoparticles and adjuvanted with the nontoxic meningococcal unlgycosylated lipid A. This novel meningococcal vaccine formulation provides the following advantages over the current meningococcal conjugate vaccine: 1- does not require chemical conjugation, 2- self adjuvanting-antigen delivery vehicle, 3- enhanced uptake by immune cells and slow antigen release, 4- induces robust autophagy formation that enhances antigen presentation, 5- heat-stable formulation that does not require refrigeration, and 6- can be administered orally or intranasally, therefore no needle use. To achieve our goal we propose the following: 1) Determine the capacity for antigen presentation by dendritic cells pulsed with meningococcal vaccine loaded nanoparticles; 2) Determine the correlates of protection in mice immunized orally or intraperitoneally with the meningococcal nanoparticle vaccine. The nanotechnology-based meningococcal vaccine is specifically suitable for endemic meningitis regions like Sub-Saharan Africa where millions of people are at risk.
