Abstract
ABSTRACTCapsular polysaccharide-protein conjugate vaccines protect individuals from invasive disease and decrease carriage, which reduces spread of the organism in the population. In contrast, antibodies elicited by plain polysaccharide or protein antigen-based meningococcal (Men) vaccines have little or no effect on decreasing carriage. In this study, we investigated the mechanism by which vaccine-induced human immunoglobulin G (IgG) antibodies affect colonization by meningococcal serogroup B (MenB) or C (MenC) strains using a human bronchial epithelial cell culture model (16HBE14o-). Fluorescence microscopy showed that bacteria colonizing the apical side of 16HBE14o- monolayers had decreased capsular polysaccharide on the bacterial surface that resulted from shedding the capsule and not decreased production of polysaccharide. Capsular polysaccharide shedding depended on the presence of 16HBE14o- cells and bacteria but not direct adherence of the bacteria to the cells. Treatment of bacteria and cells with postimmunization MenC-conjugate IgG or murine anti-MenB polysaccharide monoclonal antibodies (MAbs) inhibited capsule shedding, microcolony dispersal, and invasion of the 16HBE14o- cell monolayer. In contrast, the IgG responses elicited by immunization with MenC polysaccharide (PS), MenB outer membrane vesicle (OMV)-based, or factor H binding protein (FHbp)-based vaccines were not different than preimmune IgG or no-treatment response. The results provide new insights on the mechanism by which high-avidity anticapsular antibodies elicited by polysaccharide-conjugate vaccines affect meningococcal colonization. The data also suggest that any effect on colonization by IgG elicited by OMV- or FHbp-based vaccines may involve a different mechanism.
Highlights
Neisseria meningitidis is a bacterial species that normally colonizes human upper airway epithelial cells
The purpose of this study was to investigate, mechanistically, the effects of immunoglobulin G (IgG) antibodies elicited by a MenC PSconjugate vaccine on bacteria in a polarized airway epithelial cell model of meningococcal colonization compared to antibodies elicited by plain PS, outer membrane vesicle (OMV), and meningococcal serogroup B (MenB)-factor H binding protein (FHbp)
Using a ratio of approximately ϳ250 bacteria per 1 million epithelial cells as a reasonable approximation of human colonization, with respect to the number of epithelial cells being in large excess over the number of bacteria, 16HBE14o- cells gave the greatest and most consistent number of colonizing bacteria after 4 h of incubation, which simulates the initial stage of meningococcal colonization
Summary
Neisseria meningitidis is a bacterial species that normally colonizes human upper airway epithelial cells. Vaccines containing neisserial human complement factor H binding protein (FHbp) have been licensed in the United States [16], and they provide much broader protection than OMV vaccines against MenB strains, as well as strains from other meningococcal capsular groups. The purpose of this study was to investigate, mechanistically, the effects of IgG antibodies elicited by a MenC PSconjugate vaccine on bacteria in a polarized airway epithelial cell model of meningococcal colonization compared to antibodies elicited by plain PS, OMV, and MenB-FHbp. In the following, we show that high-avidity IgG elicited by PS-protein conjugate vaccines was unique in affecting characteristics of colonizing MenB and MenC strains that limit the ability to cause disease and to disseminate between individuals
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