Elimination of helminth infection restores HIV-1C vaccine-specific T cell responses independent of helminth-induced IL-10

Abstract

HIV-1 prevalence is highest in developing countries; similarly helminth parasites are often highly endemic in these same areas. Helminths are strong immune modulators, and negatively impact the ability of the infected hosts to mount protective vaccine-specific T cell immune responses for HIV-1 and other pathogens. Indeed, previously we found that Schistosoma mansoni infected mice had significantly impaired HIV-1C vaccine-specific T cell responses. Anthelminthics are available and inexpensive; therefore, in this study, we evaluated whether elimination of schistosome infection prior to vaccination with an HIV-1C DNA vaccine would increase recipients vaccine-specific responses. As expected, splenocytes from S. mansoni infected mice produced significantly elevated amounts of interleukin (IL)-4 and IL-10, and significantly lower amounts of interferon (IFN)-γ than splenocytes from naïve mice. Following elimination of parasites by praziquantel (PZQ) treatment, splenomegaly was significantly reduced, though splenocytes produced similar or higher levels of IL-10 than splenocytes from infected mice. However, we found that PZQ treatment significantly increased levels of IFN-γ in response to concanavalin A or SEA compared to splenocytes from untreated mice. Importantly, PZQ treatment resulted in complete restoration of HIV-1C vaccine-specific T cell responses at 8 weeks post-PZQ treatment. Restoration of HIV-1C vaccine-specific T cell responses following elimination of helminth infection was time dependent, but surprisingly independent of the levels of IL-4 and IL-10 induced by parasite antigens. Our study shows that elimination of worms offers an affordable and a simple means to restore immune responsiveness to T cell based vaccines for HIV-1 and other infectious diseases in helminth endemic settings.