Abstract
An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials.
Highlights
Several key advances in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) research have been made possible by the extensive use of non-human primates (NHP) as models for virus infection, vaccine evaluation and disease treatment
We draw heavily on NHP studies to provide an overview of different approaches used to assess cellular and humoral immune responses elicited by mucosal HIV/SIV vaccines, the contribution of different mucosal immunization routes to induction of protective immune responses and current progress in the development of mucosal vaccines against SIV/HIV
Not applied yet to the SIV macaque model for mucosal vaccine evaluation, analysis of human cervical secretions for immunoregulatory cytokines has been performed by multiplex assay, requiring only small volumes of sample [32,43,44] and providing additional information regarding innate and adaptive immune responses associated with protective efficacy
Summary
Several key advances in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) research have been made possible by the extensive use of non-human primates (NHP) as models for virus infection, vaccine evaluation and disease treatment. While a combination of mucosal and systemic vaccination might improve protection with regard to both blocking virus transmission and preventing systemic dissemination, the optimal route for delivery of mucosal vaccines is problematic, and may differ according to vaccine vehicle. In this regard, studies in NHP are invaluable in assessing mucosal immunization routes and comparing multiple vaccine platforms. We draw heavily on NHP studies to provide an overview of different approaches used to assess cellular and humoral immune responses elicited by mucosal HIV/SIV vaccines, the contribution of different mucosal immunization routes to induction of protective immune responses and current progress in the development of mucosal vaccines against SIV/HIV.
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