title: Successful vaccination against Leishmania donovani infection in Indian langur using alum-precipitated autoclaved Leishmania major with BCG.
abstract: Autoclaved Leishmania major (ALM) along with BCG, presently undergoing phase II clinical trial by WHO for its vaccine potential against cutaneous leishmaniasis, has been successfully evaluated in single and triple dose schedules against L. donovani in Indian langurs (Presbytis entellus). Encouraged with the results, another formulation alum-precipitated ALM (provided by WHO) along with BCG has been evaluated in this system. Eight monkeys were vaccinated with alum-precipitated ALM + BCG (1 mg of each per animal) while four were kept as unvaccinated controls. All were challenged with 100 x 10(6) amastigotes i.v. on day 60 post vaccination. Parasitic assessment in splenic tissue was performed on day 45, 90 and 180 p.c. Initially, seven of the eight vaccinated monkeys developed infection (two to six amastigotes per 1000 cell nuclei), which resolved by day 180 p.c., while the eighth monkey had a parasite burden of 14 amastigotes per 1000 cell nuclei on day 45 p.c. and died on day 130 p.c. On the other hand, there was progressive infection in unvaccinated control animals and three out of four died between days 110 and 120 p.c., and one monkey, which had low parasite burden, died on day 178 p.c. Prior to challenge, there was an initial rise in antileishmanaial antibodies in the vaccinated group compared to the unvaccinated control group, which later came down to normal level, while it remained higher in the unvaccinated control group. An increasing pattern of antigen-specific proliferative responses and interferon-gamma level to the two antigens--autoclaved L. donovani (ALD) and ALM--was observed in vaccinated monkeys throughout the experiment. There was a good correlation between parasite burden and IFN-gamma level on days 90 and 180 p.c., indicating IFN-gamma response as a sensitive parameter of immune status. The findings suggest alum-precipitated ALM+BCG as a potential vaccine against visceral leishmaniasis and warrants clinical trials.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, P.O. Box 173, 226001, Lucknow, India.
authors.forename: A
authors.initials: A
authors.lastname: Misra
authors.forename: A
authors.initials: A
authors.lastname: Dube
authors.forename: B
authors.initials: B
authors.lastname: Srivastava
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: J K
authors.initials: JK
authors.lastname: Srivastava
authors.forename: J C
authors.initials: JC
authors.lastname: Katiyar
authors.forename: S
authors.initials: S
authors.lastname: Naik
mesh_terms: D000534:Alum Compounds; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage; D001500:BCG Vaccine / Q000008:administration & dosage; D002520:Cercopithecidae; D011232:Chemical Precipitation; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D018320:Leishmania major / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D008297:Male; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000302:isolation & purification; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification
chemical_list: D000534:Alum Compounds; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001500:BCG Vaccine; D016052:Protozoan Vaccines; D015164:Vaccines, Inactivated; D003208:Concanavalin A; C041524:aluminum sulfate; D007371:Interferon-gamma