Research priorities for diarrhoeal disease vaccines: memorandum from a WHO meeting.
WHO's Programme for Control of Diarrheal Diseases (CDD) promoted and supported research the purpose of which is to develop and evaluate vaccines against diarrheal diseases, but it focused on diarrhea control. In 1991, the WHO/UNDP Programme for Vaccine Development (PVD) began coordinating diarrheal disease vaccine research, yet CDD remained actively involved in vaccine trials. In March 1991, CDD and PVD cosponsored a meeting to specify new research priorities toward vaccines against rotaviruses, Shigella, cholera, and enterotoxigenic Escherichia coli (ETEC) infections. Synopses of clinical trials on vaccines that have undergone clinical trials are presented. Different methods of developing vaccines against rotavirus included heterologous rotavirus adapted to tissue cultures, incorporating the VP7 surface protein of human rotaviruses into an animal rotavirus, and naturally attenuated. Live oral vaccines, different ways to immunize with oral encapsulated antigens, and a gycoconjugate approach comprised the Shigella vaccine research. There were many candidate Shigella vaccines which the meeting participants found to be promising and challenging. Cholera vaccines included killed and live oral vaccines. The results of a large field trial of cholera vaccines (killed whole cell/B subunit and whole cell culture) in Bangladesh revealed marked improvements over injected vaccines. A study of children in Indonesia showed promise for strain CVD-103HgR as a 1 dose, live oral vaccine against cholera. Adult volunteers who received milk immunoglobulin concentrate with antibodies against several colonization factor fimbriae (LT and O antigens) and then challenged experimentally with ETEC were 100% protected. WHO emphasized the need to develop both living and nonliving oral ETEC vaccines which will grant broad spectrum immunity to young children. Specific recommendations follow each section on the various vaccines and general recommendations are included.