Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections

Zhan, Bin; Beaumier, Coreen M; Briggs, Neima; Jones, Kathryn M; Keegan, Brian P; Bottazzi, Maria Elena; Hotez, Peter J

Since five of these six antigens listed in TABLE 2 are the major antigens recognized by protective immune sera induced by living UV-attenuated eggs, we are now comparing them for protective efficacy while simultaneously determining the requirements for additional antigen discovery. In order to down-select an appropriate antigen(s) for further development, these recombinant antigens will be compared in a mouse challenge model. The recombinant proteins will be produced in an appropriate expression system (i.e., bacteria, yeast or baculovirus) and used as immunogens for immunogenicity studies and vaccine trials in a mouse model. In parallel, a proteomics approach will be undertaken to evaluate additional ES and surface proteins from A. suum for their immunoreactivity to immune serum from the pig model as a backup strategy for identification of vaccine candidates. The goal is to rank the top two candidate antigens with respect to their efficacy in a preclinical challenge model, together with the ability to express these antigens as soluble proteins in high yield (see below). The corresponding antigens from A. lumbricoides will also be cloned and expressed and examined for immunological cross-reactivity.