Failure of a multi-subunit recombinant leishmanial vaccine (MML) to protect dogs from Leishmania infantum infection and to prevent disease progression in infected animals
- 作者：L. Gradoni ; V. Foglia Manzillo ; A. Pagano ; D. Piantedosi ; R. De Luna ; M. Gramiccia ; A. Scalone ; T. Di Muccio and G. Oliva
- 关键词：Recombinant polyprotein ; Leishmania ; Canine leishmaniasis ; Vaccine
- 刊名：Vaccine
- 出版年：2005
- 期刊代码：89_0264410x
- 类别：imm
- 出版时间：2005
- 卷：23
- 期：45
- 页码：5245-5251
- 文件大小：195 K
摘要
We report results of a Phase III trial of the multi-subunit recombinant Leishmania polyprotein MML for the protection of dogs against infection by Leishmania infantum. The antigen, also known as Leish-111f, is the first antileishmanial human vaccine entered Phase I clinical testing. The study was performed in a leishmaniasis endemic area of southern Italy. Three groups of 15 Leishmania-free beagle dogs each, received 3 monthly injections with vaccines A (MML + MPL®-SE adjuvant), B (sterile saline = control) and C (MML + Adjuprime adjuvant), respectively, before transmission season 2002. The surviving dogs received a second three-dose vaccine course 1 year later. The dogs were naturally exposed to sandfly bites for 2.5 months in 2002, and for 5 months in 2003. Every 2 months post vaccination, dogs were examined by clinical and immunological evaluation, and by specific serology, microscopy, culture and PCR. A weak lymphoproliferative response to MML was seen in A and C groups throughout the study period. One year after the first vaccine course, the cumulative incidence of leishmanial infections was 40%in group A, 43%in group B and 36%in group C. Two-year post-vaccination (1 year after the second vaccine course) the cumulative incidence was 87%in group A (with three symptomatic cases), 100%in group B (with no symptomatic cases) and 100%in group C (with two symptomatic cases). The efficacy of the MML vaccine as an immunotherapeutic agent for the prevention of disease progression (subpatent infection → asymptomatic patent infection → symptomatic patent infection) was evaluated through follow-up of dogs found infected prior to the second vaccination. Among 15 infected animals, progression to a subsequent stage of infection was found in 5/6 dogs of group A, 3/6 of group B and 2/3 of group C. We conclude that vaccination with MML is not effective to prevent leishmaniasis infection and disease progression in dogs under field conditions.