The generation of an efficacious vaccine that elicits protective CD4+ T cell-mediated immunity has been elusive. The lack of a vaccine against the Leishmania parasite is particularly perplexing as infected individuals acquire life-long immunity to reinfection. Experimental observations suggest that the relationship between immunological memory and protection against Leishmania is not straightforward and that a new paradigm is required to inform vaccine design. These observations include: (i) induction of Th1 memory is a component of protective immunity, but is not sufficient; (ii) memory T cells may be protective only if they generate circulating effector cells prior to, not after, challenge; and (iii) the low-dose/high-inflammation conditions of physiological vector transmission compromises vaccine efficacy. Understanding the implications of these observations is likely key to efficacious vaccination.
Keywords: CD4(+) T cells; Leishmania; concomitant immunity; immune memory; inflammation; vaccination.
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