Emory Vaccine Center
Charles Howard Candler Professor
Department of Pathology and Laboratory Medicine, Emory University School of Medicine
Yerkes National Primate Research Center
Emory Center for AIDS Research
TDr. Pulendran is a Professor in the Department of Pathology and Laboratory Medicine of the Emory University School of Medicine. He received his Ph.D. in immunology from the Walter & Eliza Hall Institute of the University of Melbourne, Victoria, Australia, and did his post-doctoral training at Immunex Corporation in Seattle, Washington.
The overall goal of our research is to understand how the innate immune system regulates adaptive immune responses to pathogens and, harness this knowledge in the design of vaccines and therapeutics. Towards this end, we are using an integrative systems biological approach that use high throughput assays (transcriptomics, micro RNA expression, metabolomics) combined with computational approaches, in the following intertwined areas of research:
1) Dendritic cell control of adaptive immunity. The innate immune system plays a central “decision-making” role in orchestrating the strength, quality and persistence of the antigen-specific T and B cell responses. Whilst the mechanisms underlying the innate control of T-helper 1 and T helper 17 responses are well studied, how T helper 2 responses against allergens and parasitic infections are induced remain poorly understood. Furthermore, the mechanisms of innate control of T regulatory responses remain a mystery. We are currently investigating the signaling networks and transcription factors in dendritic cells that orchestrate Th2 responses to allergens, and T regulatory responses. Other efforts are directed at exploring the innate control of antibody responses.
2. Innate control of “self” – “non-self” discrimination in the intestine. A remarkable feature of the immune system is its ability to launch robust immunity against pathogens, whilst remaining “tolerant” to the body’s own tissues and the trillions of commensal bacteria that colonize our intestines. To understand the mechanisms underlying this dichotomy, we are exploring the signaling networks and transcription factors that program tolerogenic antigen presenting cells in the intestine. In addition we are studying the molecular mechanisms by which nutritional sensing in the gut is coupled to intestinal inflammation and immunity.
3. Learning immunology from vaccination. A major challenge in vaccinology is that the efficacy of vaccination can only be known retrospectively, after exposure to infection. Recently, our group has pioneered a systems biological approach to identify "molecular signatures" induced early after vaccination in humans, that capable of predicting the later immune response. This study demonstrates the utility of this approach predicting vaccine efficacy, and is currently being extended to other human vaccines. The emerging data are yielding new insights about the molecular mechanisms of innate control of adaptive immunity.
In related work, we have designed synthetic vaccines that recapitulate one of the most salient features of successful live vaccines: the ability to induce persistent antibody responses that last a lifetime. We designed a synthetic nanoparticle based vaccine that resembled a virus in size and composition (multiple TLRs). Such particles induced lifelong antibody responses in mice. We are currently performing experiments in non-human primates to assess the efficacy of these nanoparticles in inducing protective immunity against HIV and malaria.