Infection with Leishmania causes significant morbidity and mortality worldwide. The type of Leishmania species infecting the host and the immune response generated by the host determines the spectrum of clinical disease that is seen. In particular, the pattern of cytokine production from T cells is critical for protection. At present there is no vaccine for Leishmania that is easy to administer, efficacious, and cost effective. These experiments will seek to establish a vaccine regimen that is sufficient to confer long-term protective immunity following infectious challenge in mice and primates. Experiments will specifically focus on DNA, protein and recombinant viral vaccines. In addition, these studies will evaluate the cellular and molecular mechanisms by which different vaccine formulations induce long-term protective cellular immunity. Over the past year we have determined the following. 1. Antigen dose and the amount of TLR adjuvant (CpG) influence the magnitude and quality of Th1 responses. 2. Gene expression profiling of antigen specific Th1 responses from three distinct vaccines that elicited protection showed striking differences suggesting there is not a common genomic signature.
|Darrah, Patricia A; Hegde, Sonia T; Patel, Dipti T et al. (2010) IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform. J Exp Med 207:1421-33|
|Lindsay, Ross W B; Darrah, Patricia A; Quinn, Kylie M et al. (2010) CD8+ T cell responses following replication-defective adenovirus serotype 5 immunization are dependent on CD11c+ dendritic cells but show redundancy in their requirement of TLR and nucleotide-binding oligomerization domain-like receptor signaling. J Immunol 185:1513-21|
|Lindenstrom, Thomas; Agger, Else Marie; Korsholm, Karen S et al. (2009) Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J Immunol 182:8047-55|