Improving virus-specific immunity by IFN-I modulation

Palacio Betancur, Nicole Maria

doi:https://doi.org/10.21985/n2-xspb-1j48

Work

Improving virus-specific immunity by IFN-I modulation

Public

Download PDF

Download All Files (.zip)

Vaccines, such as those against smallpox virus, polio virus, and yellow fever virus, have saved millions of lives. However, many infectious diseases, such as HIV-1, still lack a preventive vaccine. In addition, various vaccines, such as those against Influenza and SARS-CoV-2 require boosters and may not confer 100% lifelong protection against infection. This poses an urgent need to improve our current, as well as our future vaccines in order to improve global health. Vaccines work by inducing the development of innate and adaptive immune responses. Cytokines are proteins that serve as critical orchestrators of immune responses. An important cytokine during viral infection are Type I interferons (IFN-I). IFN-I participate in the regulation of both innate and adaptive immune responses, and these cytokines promote acute viral control within hours of infection. IFN-I signaling on T cells is required for their survival, clonal expansion, and memory generation. Although critical, the immune system needs to modulate IFN-I levels for optimal responses. Absence of IFN-I signaling during an acute viral infection dampens the immune response and leads to chronic infection, whereas during chronic infection, constitutive IFN-I signaling can play a detrimental role by promoting immune exhaustion. Since the effects of IFN-I on adaptive immunity have been studied by long-term ablation of this pathway, the effects of early IFN-I responses in the generation of adaptive immunity remained understudied. Here, we show that acute IFN-I blockade following viral immunization improves vaccine immunogenicity. Transient blockade of this pathway results in superior adaptive immune responses and protection against future infections. Through the elucidation of the early effects of IFN-I we have developed a novel strategy to increase the efficacy to viral vaccines.

Creator