Immunizing humanised mice with outer membrane vesicles from Acinetobacter baumannii to study antigen recognition and vaccine development

Adam Cunningham

Professor Adam Cunningham
Professor of Functional Immunity 
Institute of Immunology and Immunotherapy, University of Birmingham (UK)

Collaborators:

Dr Stephen Reece, Kymab Ltd (UK)
Prof Paul Kellam, Kymab Ltd (UK)
Prof Ian Henderson, Institute for Molecular Bioscience (Australia) 

Summary

Most vaccines that work in humans work through antibodies. Identifying antibodies present in human sera after previous exposure to a pathogen or a toxin has been a valuable way to identify new vaccine candidates (antigens) recognised by humans. This has been invaluable for guiding vaccine design as part of a process called “reverse vaccinology”. Nevertheless, it has significant limitations, not least because vaccination artificially “skews” the antibody response, something not possible to detect in normal human sera after natural infection. The Kymab mouse, overcomes this limitation by replacing mouse antibody genes with human antibody genes. This means we can immunise mice to identify what parts of an antigen are recognised by humanised antibodies. This will lead us to examine how human antibodies “see” antigen to provide protection from a vaccine. This can accelerate vaccine design and development and reduce costs in vaccine development. This is a major reason Kymab has attracted significant investment from organisations like Wellcome and BMGF. We will test the potential of outer membrane vesicles from Acinetobacter baumannii to induce protective antibodies against infections with this organism. This pathogen is a significant cause of hospital-acquired infections in high and LMICs and shows significant resistance to multiple antibiotics. We will examine the strength of binding of the antibodies induced to distinct antigens within the OMV and the comparative capacity of the antibodies induced to kill Acinetobacter baumannii bacteria. This is the first step to developing a new vaccine targeted to populations most at risk of Acinetobacter baumannii infection.