Meningococcal Omp85 in Detergent‐Extracted Outer Membrane Vesicle Vaccines Induces High Levels of Non‐Functional Antibodies in Mice

Abstract

The vaccine potential of meningococcal Omp85 was studied by comparing the immune responses of genetically modified deoxycholate-extracted outer membrane vesicles, expressing five-fold higher levels of Omp85, with wild-type vesicles. Groups (n = 6-12) of inbred and outbred mouse strains (Balb/c, C57BL/ 6, OFI and NMRI) were immunized with the two vaccines, and the induced antibody levels and bactericidal and opsonic activities measured. Except for Balb/ c mice, which were low responders, the genetically modified vaccine raised high Omp85 antibody levels in all mouse strains. In comparison, the wild-type vaccine gave lower antibody levels, but NMRI mice responded to this vaccine with the same high levels as the modified vaccine in the other strains. Although the vaccines induced strain-dependent Omp85 antibody responses, the mouse strains showed high and similar serum bactericidal titres. Titres were negligible with heterologous or PorA-negative meningococcal target strains, demonstrating the presence of the dominant bactericidal PorA antibodies. The two vaccines induced the same opsonic titres. Thus, the genetically modified vaccine with high Omp85 antibody levels and the wild-type vaccine induced the same levels of functional activities related to protection against meningococcal disease, suggesting that meningococcal Omp85 is a less attractive vaccine antigen.

Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria

“…Hence, insights gained from studies of OMP folding and biogenesis are also vital for our understanding of human physiology ( 83 ) and will be key in guiding our choice of targets for the generation of new antibiotics and vaccines against Gram-negative bacteria ( 84 ). Consequently, a number of academic groups and drug companies have ongoing research projects targeting the essential OMPs BamA (the central β-barrel-containing subunit of BAM) and LptD ( 80 , 82 , 85 – 92 ), with at least six reports of inhibitors of their function in 2018-2019 alone ( 93 – 98 ).…”

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

“…Omp85, a highly conserved protein essential for the proper positioning and folding of OMPs in the bacterial membrane, has been hypothesized to be the reactive 80-kDa protein observed in immunoblots probed with antisera from individuals vaccinated with the Norwegian OMV 16 , 56 . Despite its immunogenicity, when Omp85 was overexpressed in meningococcal OMV it failed to induce higher bactericidal antibodies compared to wild-type vesicles in mice 57 . Thus, Omp85 appeared to be poorly bactericidal on its own.…”