Agonistic Anti-CD40 Enhances the CD8(+) T Cell Response during Vesicular Stomatitis Virus Infection

Intracellular pathogens are capable of inducing vigorous CD8(+) T cell responses. However, we do not entirely understand the factors driving the generation of large pools of highly protective memory CD8(+) T cells. Here, we studied the generation of endogenous ovalbumin-specific memory CD8(+) T cells following infection with recombinant vesicular stomatitis virus (VSV) and Listeria monocytogenes (LM). VSV infection resulted in the generation of a large ovalbumin-specific memory CD8(+) T cell population, which provided minimal protective immunity that waned with time. In contrast, the CD8(+) T cell population of LM-ova provided protective immunity and remained stable with time. Agonistic CD40 stimulation during CD8(+) T cell priming in response to VSV infection enabled the resultant memory CD8(+) T cell population to provide strong protective immunity against secondary infection. Enhanced protective immunity by agonistic anti-CD40 was dependent on CD70. Agonistic anti-CD40 not only enhanced the size of the resultant memory CD8(+) T cell population, but enhanced their polyfunctionality and sensitivity to antigen. Our data suggest that immunomodulation of CD40 signaling may be a key adjuvant to enhance CD8(+) T cell response during development of VSV vaccine strategies.