MilliporeSigma
  • Home
  • Search Results
  • A broadly-protective vaccine against meningococcal disease in sub-Saharan Africa based on generalized modules for membrane antigens (GMMA).

A broadly-protective vaccine against meningococcal disease in sub-Saharan Africa based on generalized modules for membrane antigens (GMMA).

Vaccine (2014-04-08)
Oliver Koeberling, Emma Ispasanie, Julia Hauser, Omar Rossi, Gerd Pluschke, Dominique A Caugant, Allan Saul, Calman A MacLennan
ABSTRACT

Neisseria meningitidis causes epidemics of meningitis in sub-Saharan Africa. These have mainly been caused by capsular group A strains, but W and X strains are increasingly contributing to the burden of disease. Therefore, an affordable vaccine that provides broad protection against meningococcal disease in sub-Saharan Africa is required. We prepared Generalized Modules for Membrane Antigens (GMMA) from a recombinant serogroup W strain expressing PorA P1.5,2, which is predominant among African W isolates. The strain was engineered with deleted capsule locus genes, lpxL1 and gna33 genes and over-expressed fHbp variant 1, which is expressed by the majority of serogroup A and X isolates. We screened nine W strains with deleted capsule locus and gna33 for high-level GMMA release. A mutant with five-fold increased GMMA release compared with the wild type was further engineered with a lpxL1 deletion and over-expression of fHbp. GMMA from the production strain had 50-fold lower ability to stimulate IL-6 release from human PBMC and caused 1000-fold lower TLR-4 activation in Human Embryonic Kidney cells than non-detoxified GMMA. In mice, the GMMA vaccine induced bactericidal antibody responses against African W strains expressing homologous PorA and fHbp v.1 or v.2 (geometric mean titres [GMT]=80,000-200,000), and invasive African A and X strains expressing a heterologous PorA and fHbp variant 1 (GMT=20-2500 and 18-5500, respectively). Sera from mice immunised with GMMA without over-expressed fHbp v.1 were unable to kill the A and X strains, indicating that bactericidal antibodies against these strains are directed against fHbp. A GMMA vaccine produced from a recombinant African N. meningitidis W strain with deleted capsule locus, lpxL1, gna33 and overexpressed fHbp v.1 has potential as an affordable vaccine with broad coverage against strains from all main serogroups currently causing meningococcal meningitis in sub-Saharan Africa.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Mouse IL-6 ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Mouse IL-6 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Human IL-6 sR ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Phosphatase substrate, powder
Sigma-Aldrich
4-Nitrophenyl phosphate disodium salt hexahydrate, tablet
Sigma-Aldrich
4-Nitrophenyl phosphate disodium salt hexahydrate, powder, BioReagent, suitable for cell culture, ≥97%
Sigma-Aldrich
4-Nitrophenyl phosphate disodium salt hexahydrate, tablet
Sigma-Aldrich
4-Nitrophenyl phosphate disodium salt hexahydrate, tablet
Sigma-Aldrich
Cytidine-5′-monophospho-N-acetylneuraminic acid sodium salt, ≥85% (HPLC)
Sigma-Aldrich
4-Nitrophenyl phosphate disodium salt hexahydrate, suitable for enzyme immunoassay, ≥99.0% (enzymatic)
Sigma-Aldrich
Phosphatase substrate, 100 mg capsules
Sigma-Aldrich
Phosphatase substrate, 5 mg tablets
Sigma-Aldrich
Phosphatase substrate, 40 mg tablets
Sigma-Aldrich
Phosphatase substrate, 40 mg capsules
Sigma-Aldrich
Phosphatase substrate, Suitable for manufacturing of diagnostic kits and reagents
Sigma-Aldrich
Human IL-6 ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Rat Interleukin-6 ELISA Kit, for for cell lysate and tissue lysate
Sigma-Aldrich
Human IL-6 ELISA Kit, for cell and tissue lysates
Sigma-Aldrich
Rat IL-6 ELISA Kit, for serum, plasma and cell culture supernatants
Sigma-Aldrich
Mouse IL-6 R ELISA Kit, for serum, plasma and cell culture supernatant