Challenges in mucosal HIV vaccine development: lessons from non-human primate models.

An efficacious HIV vaccineis urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trialin Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosalsurfaces, development of immunity at these sites is critical, but few clinical vaccine trialshave targeted these sites or assessed vaccine-elicited mucosalimmune responses. Pre-clinical studies in non-humanprimate models have facilitated progress in mucosalvaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosalsamples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-humanprimate studies which have provided important information for future design of vaccine strategies, targeting of mucosalinductive sites, and assessment of mucosalimmunity. Knowledge gained in these studies will inform mucosalvaccine design and evaluation in human clinical trials.