Adapting the innate immune system to develop long-lived vaccines to bacterial pathogens

Abstract

There is an urgent need to develop vaccines against bacteria due to the rise of Multi-drug resistant (MDR & XDR) organisms. To date, it has been difficult to produce protective vaccines against bacterial pathogens; there is a danger of outgrowth of fast growing attenuated bacterial strains while polysaccharide cell walls are poorly immunogenic and subunit vaccines are ineffective, generating TI (T-independent) immune responses, characterized by low affinity, short lived, non-class switched IgM antibodies. We are developing technologies for generating vaccines in mice against multiple pathogen species, including bacterial; MDR E. coli, MRSA, MTb LAM, Viral; HIV gp120, parasitic; P. falciparum and fungal; C. albicans. We capture pathogens using FcMBL Opsonin technology (which binds more than 90 different pathogen species), and present the killed pathogens in an immune modulating biomaterial system. This lyophilized product provides long-lasting protection with a single dose through a novel self-boosting mechanism of action. Our vaccines can protect mice against MDR strains of E. coli which are lethal within 12 hours. We have raised antibodies with titers which are sustained beyond 90 days (to date) with a single vaccination (the biomaterial system has demonstrated titers beyond 1 year in other indications). Using this opsonin and immune modulating technology, E. coli can be captured from the blood and tissues of one animal and used to vaccinate other animals.