ILiAD Biotechnologies lead candidate is BPZE1, a live attenuated Bordetella pertussis (BP) vaccine.  Natural clinical BP Infection induces sterilizing mucosal immunity and long-lasting protection against pertussis disease.  Similarly, nasally administered BPZE has been designed for long lasting immunity and the ability to induce both mucosal and systemic potent immune responses. This may result in broader BP immunity compared to parenteral vaccines.

Over the past ten years, Dr Camille Locht has led the development of an attenuated vaccine strain based on knowledge of the specific molecular mechanisms of pertussis pathogenesis. The latest version of this vaccine strain, named BPZE1, contains genetic alterations that eliminate or inactivate three different B. pertussis toxins. In BPZE1 the dermonecrotic toxin gene is deleted, and the pertussis toxin (PT) gene is genetically modified by altering two different codons, so that the enzymatic ADP-riboslyltransferase activity of the toxin is abolished, yielding to a fully inactive protein. Finally, the B. pertussis ampG gene is replaced by E. coli ampG, which results in virtual absence of the tracheal cytotoxin.

The BPZE1 strain was found to be non-pathogenic in mouse models and caused no pulmonary inflammation, yet it is able to colonize the mouse respiratory tract nearly as long as the virulent parent strain. A single nasal administration of BPZE1 induces full protection against challenge with virulent B. pertussis in mice (Skerry & Mahon, 2011). BPZE1-induced protection is mediated by both antibodies and CD4⁺ T cells (Feunou et al., 2010). Protection against challenge is dose-dependent (Mielcarek et al., 2010) and is directly related to the ability of the vaccine strain to colonize the respiratory tract and to induce both anti-B. pertussis antibodies and IFN-g-secreting cells.

In pre-clinical mouse studies BPZE1 induced long-lasting protection (Feunou et al., 2010; Skerry & Mahon, 2011). For up to at least one year, a single nasal administration of BPZE1 given to adult or infant mice provided total protection against nasal challenge with virulent B. pertussis, whereas immunity induced by two administrations of acellular vaccine (aPV) started to wane at 6 months after the last immunization. Furthermore, BPZE1 vaccination induced rapid protection, which can be detected as early as a few days after immunization (Debrie et al., in preparation).