Lessons along the Critical Path: Developing Vaccines against Human Helminths

• Published in: Trends in parasitology 2018-09, Vol.34 (9), p.747-758
• Main Authors: Diemert, David J., Bottazzi, Maria Elena, Plieskatt, Jordan, Hotez, Peter J., Bethony, Jeffrey M.
• Format: Article
• Language: English
• Subjects: Helminthiasis - immunology; Helminthiasis - prevention & control; Humans; Vaccines, Subunit - standards
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2018.07.005

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. Antigen discovery for helminth vaccines has undergone exponential growth in the era of ‘omics’ and systems biology. Parallel advances have not occurred in the product and clinical development sciences that are required to take these candidate vaccines into human trials. The potential for a candidate vaccine to advance into clinical trials remains low, as these products must follow the ‘critical path’ of process development, manufacture, preclinical testing, and clinical trials. The focus of the critical path is for the vaccine candidate to meet the safety, immunogenicity, and efficacy criteria of national regulatory authorities. The critical path may be more difficult for helminth vaccines due to unique challenges in their manufacturing process, preclinical development, and clinical development.