Development of alternative vaccination strategies to overcome Tc1 vaccine failure caused by chronic schistosomiasis

Abstract

Abstract It is a global public health imperative to develop vaccine strategies that produce effective cell-mediated immunity in schistosome-endemic areas, such as sub-Saharan Africa, where HIV infection is common. Vaccine delivery techniques effective in immune-suppressed populations are critical to combating infectious diseases in these already compromised groups. It is well-known that immune suppression, such as by chronic schistosome infection, can cause Tc1/Th1 type vaccines to fail. Listeria, a strong inducer of cell-mediated immunity, can overcome the Th2 biasing and immune suppression caused by schistosome infection. However, safety concerns cause reluctance among the vaccine community and the public to incorporate this vector into immunization programs. Since neither DNA nor the Listeria vaccine vector are ideal for clinical translation, and Gag is likely not the ideal HIV vaccine antigen, we are using this system as a model for enumeration of Tc1 responses (IFNγ+ CD8+ cytotoxic T lymphocytes, CTL); CTLs are likely necessary components of functional responses for next-generation vaccines targeting diseases that currently lack effective vaccines (HIV, TB, malaria). Here, we investigate why DNA vaccine vectors fail during chronic schistosomiasis when Listeria vaccine vectors can generate robust CTL responses to HIV Gag. Specifically, we are examining live bacteria as adjuvants for an episomally expressed or concurrently administered DNA vaccine for HIV Gag. This project is one step toward our overall goal, which is to generate cell-mediated vaccine immunity in schistosome-infected, immune-suppressed patients.