Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study.
BACKGROUND
Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions.


METHODS
A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity.


RESULTS
The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL.


CONCLUSIONS
Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.
Khalil
Eltahir Awad Gasim
EA
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. eltahirk@iend.org
Musa
Ahmed Mudawi
AM
Modabber
Farroukh
F
El-Hassan
Ahmed Mohamed
AM
D000293:Adolescent; D000534:Alum Compounds; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D001500:BCG Vaccine / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008297:Male; D016052:Protozoan Vaccines / Q000009:adverse effects / Q000276:immunology*; D012882:Skin Tests; D017778:Vaccines, Combined / Q000009:adverse effects / Q000276:immunology
D000534:Alum Compounds; D000913:Antibodies, Protozoan; D001500:BCG Vaccine; D054332:Leishmaniasis Vaccines; D016052:Protozoan Vaccines; D017778:Vaccines, Combined; C416262:autoclaved Leishmania major vaccine; C041524:aluminum sulfate