Controlled human infection with Neisseria lactamica induces B-cell responses that are cross-reactive with Neisseria meningitidis

Abstract

Abstract Neisseria lactamica (Nlac) is a commensal of the human oropharynx. Colonisation with Nlac significantly reduces colonisation by N. meningitidis (Nmen). We hypothesised that cross-reactive adaptive cellular immune responses were responsible for this effect. 31 volunteers were inoculated intra-nasally with 105 colony-forming units of Nlac or vehicle control. Nlac/Nmen colonisation status was assessed at baseline and 7-, 14- and 28-days post-inoculation. Nlac/Nmen-specific plasma cells (PCs)/memory B-cells were quantified in PBMCs at all time points using ELISpot assays. Amongst Nlac-colonised volunteers (n=17), Nlac-specific PC frequencies/2×105 PBMCs increased significantly. Median baseline vs. post-colonisation peak Nlac-specific PC frequencies were 0 (range 0–0.5) vs. 2 (0–31) for IgM, 0 (0–1) vs. 5 (0–20.5) for IgA, and 0 (0–1) vs. 3 (0–27) for IgG (all p<0.0001). Nlac-specific IgG memory B-cell frequencies also increased significantly from baseline to day 28 (0.000% vs. 0.04%, p<0.0001). Interestingly, there was also a significant increase in IgM, IgA and IgG Nmen-specific PCs amongst Nlac-colonised volunteers. Median baseline vs. post-colonisation peak Nmen-specific PC frequencies were 0 (0–0) vs. 0 (0–30) for IgM, 0 (0–1) vs. 0.5 (0–8.5) for IgA, and 0 (0–0.5) vs. 0.5 (0–10) for IgG (all p≤0.01). There was no induction of Nlac-specific PCs/memory B-cells in the control group (n=10). These data suggest that the previously observed protective effect of Nlac on Nmen colonisation may have an immunological basis. We plan to assess the frequency/effector phenotype of Nlac-specific CD4+ memory T-cells following Nlac colonisation and hypothesise that cross-reactive CD4+ memory T-cells directed towards Nmen will be Th17.