Th1 concomitant immune response mediated by IFN-γ protects against sand fly delivered Leishmania infection: Implications for vaccine design

Leishmaniasis is an unresolved global health problem with a high socio-economic impact. Data generated in mouse models has revealed that the Th1 response, with IL-12, IFN-gamma, TNF-alpha, and IL-2 as prominent cytokines, predominantly controls the disease progression. Premised on these findings, all examined vaccine formulations have been aimed at generating a long-lived memory Th1 response. However, all vaccine formulations with the exception of live Leishmania inoculation (leishmanization) have failed to sufficiently protect against sand fly delivered infection. It has been recently unraveled that sand fly dependent factors may compromise pre-existing Th1 memory. Further scrutinizing the immune response after leishmanization has uncovered the prominent role of early (within hours) and robust IFN-gamma production (Th1 concomitant immunity) in controlling the sand fly delivered secondary infection. The response is dependent upon parasite persistence and subclinical ongoing primary infection. The immune correlates of concomitant immunity (Resident Memory T cells and Effector T subsets) mitigate the early effects of sand fly delivered infection and help to control the disease. In this review, we have described the early events after sand fly challenge and the role of Th1 concomitant immunity in the protective immune response in leishmanized resistant mouse model, although leishmanization is under debate for human use. Undoubtedly, the lessons we learn from leishmanization must be further implemented in alternative vaccine approaches.

Automated summary

Leishmaniasis is a global health problem with Th1 response playing a crucial role in disease control. Vaccine formulations aimed at generating long-lived memory Th1 response have not been effective against sand fly transmitted infection except for leishmanization. Recent studies have shown that sand fly dependent factors may compromise pre-existing Th1 memory, while Th1 concomitant immunity has a prominent role in controlling secondary infections delivered by sand fly.