The Leishmania (Leishmania) donovani
nucleoside hydrolase NH36 is the main
antigen of the Leishmune®
vaccine and one of the promising candidates for vaccination against
visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with L. (L.) infantum from an endemic area of
visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced
a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from
visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42-43% higher, in response to F1 than to NH36. The
interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured
cutaneous leishmaniasis after NH36 stimulation. While no
IL-10 secretion was determined by F1, a
granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the
infection by L. (L.) infantum. In addition, F1 and NH36 discriminated the
IgG3 humoral response in patients with active
visceral leishmaniasis due to L. (L.) donovani (Ethiopia) and L. (L.) infantum (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from L. (L.) donovani-infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with L. (L.) infantum chagasi, may also be involved in the generation of a protective response against L. (L.) infantum and represents a potential
vaccine candidate for the control of human
leishmaniasis alone, or in combination with other HLA
epitopes/
antigens.