Recombinant Neisseria surface protein A is a potential vaccine candidate against Neisseria meningitides serogroup B

Abstract

Neisseria meningitidis is the pathogen of epidemic encephalomyelitis and is responsible for permanent damage to the brain and nervous system. In the present study, the prokaryotic expression vector pGEX-6p-1/neisseria surface protein A (NspA) was constructed and the immune protective effect was investigated with the purified recombinant rNspA. Female BALB/c mice were immunized by intraperitoneal inoculation of rNspA, glutathione S-transferase (GST) or phosphate-buffered saline (PBS). The protection experiment in mice demonstrated that the protection rate of the rNspA group was 85% against the N. meningitidis strain MC58, and a serum bactericidal assay in vitro revealed that the serum bactericidal titer of the rNspA group reached 1:64 following three immunizations. The levels of specific immunoglobulin (Ig) A (SIgA), IgG, IgG1, IgG2a, IgG2b and IgG3 of mice in the rNspA group peaked at week six and were higher than those in the mice in the GST and PBS groups. The levels of stimulation index, interleukin-4 and interferon-γ in the culture supernatant of the spleen lymphocytes of the rNspA group increased in a time-dependent manner and were higher than those of the mice in the GST and PBS groups over the same period. The results suggested that rNspA may induce increased specific humoral and cellular immune responses, and that it is effectively protective against N. meningitidis serogroup B in mice. The present study offered novel evidence that may lead to the development of a novel effective N. meningitidis serogroup B vaccine.

OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans

“…Therefore, we can speculate that the underlying reasons for the different SBA outcomes observed in our analysis may reside in an LOS shielding effect. Lastly, Neisserial surface protein A was identified as another protective antigen contained within OMV from mice immunogenicity studies, confirming previous findings about its ability to elicit bactericidal antibodies 68 , 69 and to protect animals during in vivo meningococcal challenges 70 , 71 . In our study, only two strains, M07576 and M12898, were killed by NspA mouse antisera.…”

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

“…The vaccine pNMB0315 + CpG group and pNMB0315 group offered 70 and 65% protection against NMB MC58, respectively, two weeks following innoculation. The survival rate (70%) of pNMB0315 immunization is lower than that of rNspA immunization (85% survival rate) reported by the authors, previously (3), which might be associated with lower transfection efficiency of eukaryotic plasmid pNMB0315. Therefore, a prokaryotic expression vector will be constructed to express recombinant protein NMB0315 and research its immunocompetence and immunoprotection.…”

“…. Two weeks following the third immunization (20 mice in each group), immune serum was collected for SBA as described previously (3). Briefly, a suspension of MNB strain MC58 (40,000 CFU/ml) was mixed with newborn rabbit complement (Pel-Freez Biologicals, Rogers, AR, USA) at a 1:1 ratio; the mixture was subsequently combined with the immune serum, serially diluted in 2-fold from 1:2 to 1:256, and cultured for 1 h at 37˚C prior to being inoculated on chocolate agar plates and incubated at 37˚C overnight.…”

“…Neisseria meningitidis (N. meningitidis) is a Gram-negative microorganism and a major causative agent of severe sepsis and meningitis (1), both of which may lead to mortality in children and young adults within h, although effective antibiotics are available (2,3). N. meningitidis causes meningococcal diseases in ~500,000 people annually worldwide, mainly affecting children between the ages of 3 and 48 months, followed by adolescents (4), and although drug treatments such as penicillin are available, 10-15% of children and adolescents succumb to infection.…”

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare EffectiveNeisseria meningitidisVaccines

“…The elucidation of immunoescape strategies and genomics have enabled scholars to discover new potential vaccine candidates, like NMB0928 [ 282 ] or NMB1468 [ 283 ], FrpB/fetA [ 125 ], LbpA and LbpB [ 284 ], adhesin complex protein (ACP) [ 285 ], NspA [ 286 , 287 ], MIP [ 152 ], ZnuD [ 93 ], PilE [ 76 ] and PilQ [ 288 ], IgA protease [ 289 ], T cell stimulating protein A ( tsp A) [ 289 ], or the CP polymerase of Neisseria serogroup X [ 290 ], among others [ 291 ].…”