Bordetella Vaccinology Group (bvg)

Participation in the clinical development of BPZE1.

BPZE1 is a live attenuated nasal pertussis vaccine candidate now in late-stage clinical development in collaboration with ILiAD Biotechnologies. The vaccine was designed and constructed by the team members, has been evaluated for safety and efficacy in extensive murine studies and has now successfully completed phase 1 and 2 studies, demonstrating its safety, systemic and mucosal immunogenicity and efficacy against Bordetella pertussis infection in human adults. The vaccine is now ready to enter pivotal phase 3 studies and the team is actively involved in the design of these studies, as well as in the potency and adherence assays of the various clinical vaccine lots.

BPZE1 derivatives as biological platform for the development of multivalent nasal vaccines.

We have already shown that BPZE1 can be used to present heterologous antigens to the respiratory mucosa using the filamentous haemagglutinin (FHA) expression/secretion system. However, not all antigens are effectively produced and secreted via the FHA system. With support from the Frensh Ministry of Research, the US National Institutes of Health and the European Commission, we are therefore developing alternative systems The first system used for the expression/secretion of antigens not well secreted by the FHA system is based on the autotransporter SphB1. We have already shown that the SphB1 system can be used to present heterologous proteins (SARS-CoV2 nucleoprotein and Mycobacterium tuberculosis antigens) to the respiratory mucosa. This system is currently being optimized. A second system is based on the type 3 secretion system of B. pertussis, and we have shown that it is possible to use this system for the secretion of M. tuberculosis antigens, and that the recombinant B. pertussis vaccine strains are able to induce Th1 and Th17 immune responses in the nasal and lung tissues. In parallel, we are exploring the non-specific effects of BPZE1 and have seen that BPZE1 protects mice in an antigen-agnostic manner against influenza, invasive pneumococcal disease, respiratory syncytial virus, as well as against non-infectious inflammatory diseases, such as allergic asthma.

Mechanism of protection by maternal vaccination in mouse models

Maternal vaccination during pregnancy is currently considered the most effective way to protect newborns against pertussis disease. We use the mouse model to investigate the immune mechanism underlying the protective effect of maternal immunization. With support from the US National Institutes of Health and using humanized mice and monoclonal antibodies, we found that the human isotype is crucially important to protect neonatal mice against leukocytosis, the hallmark of severe pertussis. We also found that maternal vaccination with nasally delivered BPZE1 derivatives protects the offspring against nasal colonization via the induction of secretory IgA, while protection against lung colonization and leukocytosis depends on Fcg receptors.