Lessons along the Critical Path: Developing Vaccines against Human Helminths.

Helminthic parasites are important targets for vaccine research as they infect an estimated 1 billion people worldwide. Despite significant progress in the discovery of defined antigens as candidates for vaccines, the potential of a helminth vaccine advancing to an investigational product to be tested in humans remains as challenging as it did 50 years ago. Candidate helminth vaccines must still advance along a 'critical path' of preclinical research, vaccine process development (which includes 'chemistry, manufacturing, and controls' or CMC), current good manufacturing practice (cGMP) production of the vaccine, and clinical trials. This path is highly targeted towards meeting the safety, immunogenicity, and efficacy criteria of regulatory bodies such as the US Food and Drug Administration (FDA). For nearly 20 years our product development partnership (PDP), the Texas Children's Hospital Center for Vaccine Development (TCH-CVD), has followed the critical paths of several novel subunit vaccines for the human hookworm Necator americanus and the intestinal trematode Schistosoma mansoni. Herein, we describe the critical lessons learned along this critical path.