Oral Presentation 25th International Pathogenic Neisseria Conference 2026

Non-classical vaccine candidates for IMD identified through functional patient-derived hmAb screening (140659)

Camilla Gladstone 1 2 , Youssif M Ali 3 , Lauren Allen 4 , Steve Thomas 4 , Stephen Taylor 4 , Andrew Gorringe 5 , Ira Sabli 1 , Neha Karim 1 , Sara Procacci 1 , Ivan Campeotto 6 , Michael Levin 1 , Paul R Langford 1 , Joseph Campo 7 , Fadil A Bidmos 1
  1. Imperial College London, South Kensington, LONDON, United Kingdom
  2. Paediatrics, University of Oxford, Oxford, United Kingdom
  3. Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
  4. Pathogen Immunology Group, UK Health Security Agency, Porton Down, United Kingdom
  5. UK Health Security Agency, Porton Down, Salisbury, United Kingdom
  6. University of Nottingham, Nottingham, United Kingdom
  7. Antigen Discovery Inc, Irvine, California, USA

Previously, we demonstrated that cloning of fully human monoclonal antibodies (hmAbs) from plasmablasts of patients convalescing from invasive meningococcal disease (IMD) is a powerful approach for identifying novel vaccine candidates. We reported the cloning of 23 broadly cross-reactive anti-meningococcal hmAbs, of which 7 exhibited strong in vitro serum bactericidal activity (SBA) against strains not covered by 4CMenB, and a further 4 showed weak SBA. Two of the 7 hmAbs with strong SBA (P02-1A1 and P20-11D5) also protected female C57BL/6 wild-type mice from experimental meningococcal infection at 75% and 83% efficacy respectively; synergy between both hmAbs yielded 100% protection.

Here, we report investigations into the opsonophagocytic property of these hmAbs against the meningococcus and whether their SBA extended to the gonococcus. We further show that the target of the multi-functional P02-1A1 is a non-classical periplasmic protein involved in cell wall biogenesis, representing a novel vaccine candidate. Robust antibody responses were induced in CD1 mice following immunisation with 20ug of the purified periplasmic protein. Using computational modeling and protein sequence alignment, we predict that interactions between P02-1A1 and its target is mediated by a linear motif, which also explains the observed specific reactivity of P02-1A1 with 2 other antigens in immunoassays.

The targets of SBA hmAbs P02-5E10, P02-6E9, P09-2F2, and P12-7E2 have also been confirmed. In addition, we identified an hmAb, P11-5E11, cognate to a factor involved in meningococcal evasion of human immune effectors. This factor is a secreted protein, a class not traditionally prioritised in meningococcal vaccine discovery given the absence of surface exposure, therefore demonstrating that the RV 2.0 approach is agnostic to conventional antigen selection criteria.

At the time of submitting this abstract, the identities of these novel candidates and the predicted cognate epitopes cannot be disclosed due to ongoing intellectual property processes, expected to be completed by August 2026 (priority filing). Given successful filing, it is expected that these identities would be revealed at the Conference.