We have compared the efficacy of two
Leishmania
(
Leishmania)
major vaccines, one genetically attenuated (DHFR-TS deficient organisms), the
other inactivated [autoclaved promastigotes (ALM) with bacillus Calmete-Guérin
(BCG)], in protecting rhesus macaques (
Macaca mulatta
) against
infection with virulent
L. (L.) major. Positive antigen-specific recall
proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated
monkeys, versus 75% in ALM-plus-BCG-vaccinated animals), although none of these
animals exhibited either augmented in vitro gamma interferon (IFN-γ) production
or positive delayed-type hypersensitivity (DTH) response to the leishmanin skin
test prior to the challenge. Following challenge, there were significant differences
in blastogenic responses (p < 0.05) between attenuated-vaccinated monkeys and
naïve controls. In both vaccinated groups very low levels of antibody were
found before challenge, which increased after infective challenge. Protective
immunity did not follow vaccination, in that monkeys exhibited skin lesion at
the site of challenge in all the groups. The most striking result was the lack
of pathogenicity of the attenuated parasite, which persisted in infected animals
for up to three months, but were incapable of causing disease under the conditions
employed. We concluded that both vaccine protocols used in this study are safe
in primates, but require further improvement for vaccine application.
