Non-human primates as a model for understanding the mechanism of action of toll-like receptor-based vaccine adjuvants

- TLR based adjuvants increase immunogenicity of non-live vaccines.
- NHP cell subset phenotype and TLR expression reflects humans.
- NHP model better translates immunogenicity of TLR adjuvants to clinic.
- TLR adjuvants can fine tune innate immune activation.
- TLR stimulation increases T and B cell magnitude and breadth in NHPs.

While transgenic mouse models are powerful for understanding how the immune system is manipulated by vaccines, they cannot fully recapitulate the characteristics of the innate immune responses leading to adaptive immunity after vaccination in humans. Outbred non-human primates are far more representative models of human vaccine responses as there is high degree of similarities in immune cell subset distributions, receptor expression (including toll-like receptors; TLRs), and immune cell functions, in addition to modeling doses and injection sites more accurately. Vaccine adjuvants targeting TLRs have shown great promise in their ability to enhance responses to non-live vaccines. As TLR ligands are molecularly defined, studies of the mechanisms by which they interact with the immune system are facilitated. In this brief review, we focus on the use of TLR3, 4, 7/8 and 9 stimulating adjuvants in NHPs by evaluating similarities between the specified TLRs in human and NHPs and highlighting recent work studying the mode of action or efficacy of TLR based adjuvants in NHPs.