Alum-precipitated autoclaved Leishmania major plus bacille Calmette-Guérrin, a candidate vaccine for visceral leishmaniasis: safety, skin-delayed type hypersensitivity response and dose finding in healthy volunteers

Abstract

In a previous efficacy study, autoclaved Leishmania major (ALM) + bacille Calmette-Guérrin (BCG) vaccine was shown to be safe, but not superior to BCG alone, in protecting against visceral leishmaniasis. From June 1999 to June 2000, we studied the safety and immunogenicity of different doses of alum-precipitated ALM + BCG vaccine mixture administered intradermally to evaluate whether the addition of alum improved the immunogenicity of ALM. Twenty-four healthy adult volunteers were recruited and sequentially allocated to receive either 10 microg, 100 microg, 200 microg, or 400 microg of leishmanial protein in the alum-precipitated ALM + BCG vaccine mixture. Side effects were minimal for all doses and confined to the site of injection. All volunteers in the 10 microg, 100 microg, and 400 microg groups had a leishmanin skin test (LST) reaction of > or = 5 mm by day 42 and this response was maintained when tested after 90 d. Only 1 volunteer out of 5 in the 200 microg group had a LST reaction of > or = 5 mm by day 42 and the reasons for the different LST responses in this group are unclear. This is the first time that an alum adjuvant with ALM has been in used in humans and the vaccine mixture was safe and induced a strong delayed type hypersensitivity (DTH) reaction in the study volunteers. On the basis of this study we suggest that 100 1 microg of leishmanial protein in the vaccine mixture is a suitable dose for future efficacy studies, as it induced the strongest DTH reaction following vaccination.

Vaccine candidates for leishmaniasis: A review

“…However, its alum-absorbed preparation (alum-ALM) along with BCG was shown to be more immunogenic, protective and produced a strong and long-lasting Th1 response in mice, monkeys and dogs against visceral leishmaniasis [79,88,89] but it did not produce conclusive results in humans [90][91][92].…”

Leishmaniavaccines: progress and problems

“…With this in mind, a vaccine consisting of autoclaved L. major and BCG was used and shown to be safe, and significantly, it induced IFN-c production in healthy volunteers (Satti et al 2001). Alum precipitation of L. major improved the immunogenicity of the vaccine and induced a strong delayed type hypersensitivity (DTH) reaction in volunteers (Kamil et al 2003). Successful protection against L. donovani infection has been achieved with killed L. major in simian, canine and hamster models (Misra et al 2001 ;Srivastava et al 2003 ;) and provides the basis for further human trials.…”

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

“…Remarkable levels of TNF-α and IFN-γ induced by groups vaccinated with antigen containing Alum-BCG and MISA indicates the superiority of these adjuvants in the selective induction of Th1 immune responses. Alum-BCG has been indicated to induce strong Th1 immune responses in Leishmania vaccine studies (MISRA et al, 2001;KAMIL et al, 2003). In malaria, HIV and cancer vaccine studies, MISA 720 has been indicated to induce high Th1 immune responses important for the control of these diseases (KENNEY & ELDELMAN, 2003).…”