Construction and protective immunogenicity of DNA vaccine pNMB0315 against Neisseria meningitidis serogroup B

Wu,Xiaoxia; Li,Kaiming; Xie,Meihua; Yu,Minjun; Tang,Shuangyang; Li,Zhenyu; Hu,Sihai

doi:10.3892/mmr.2017.8255

Construction and protective immunogenicity of DNA vaccine pNMB0315 against Neisseria meningitidis serogroup B

Authors:
- Xiaoxia Wu
- Kaiming Li
- Meihua Xie
- Minjun Yu
- Shuangyang Tang
- Zhenyu Li
- Sihai Hu
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Affiliations: Laboratory of Anti‑infectious Immunity, Pathogenic Biology Institute, College of Basic Medicine, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: December 12, 2017 https://doi.org/10.3892/mmr.2017.8255
Pages: 3178-3185

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Abstract

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‑γ 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.

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