Construction And Protective Immunogenicity Of Dna Vaccine Pnmb0315 Against Neisseria Meningitidis Serogroup B

Neisseria meningitidis (N. meningitidis) is a major cause of meningitis and sepsis. Capsular polysaccharide-based vaccines against serogroups A, C, Y, and W135 are available; however, the development of a vaccine against N. meningitidis serogroup B (NMB) has been problematic. NMB0315 is an outer membrane protein of NMB that may be a virulence factor for N. meningitidis and a possible target for functional bactericidal antibodies. The present study aimed to develop a potent DNA vaccine against NMB by cloning the NMB0135 gene into the pcDNA3.1(+) vector to construct the recombinant plasmid pcDNA3.1(+)/NMB0315 (designated pNMB0315). pNMB0315 was transfected into eukaryotic COS-7 and RAW264.7 cells to express the recombinant (r) NMB0315 protein. Protective immunogenicity of the DNA vaccine was assessed in an in vivo mouse model. The levels of rNMB0315-specific immunoglobulin G (IgG), IgG1 and IgG2a antibodies in the pNMB0315-immunized group increased dramatically up to week 6 following the initial vaccination, and were significantly higher compared with the levels in the Control groups. The serum concentrations of interleukin-4 and interferon-gamma were significantly higher in the pNMB0315-immunized group compared with the control groups. Following intraperitoneal challenge with a lethal dose of NMB strain MC58, the survival rate in the pNMB0315 + CpG group was 70% (14 out of 20 mice) at 14 days; by contrast, all mice in the control groups succumbed within 3 days. The serum bactericidal titers of the pNMB0315 + CpG group in vitro reached 1: 128 following three immunizations. The results indicated that pNMB0315 may serve as a promising DNA vaccine against NMB.