title: Failure of a multi-subunit recombinant leishmanial vaccine (MML) to protect dogs from Leishmania infantum infection and to prevent disease progression in infected animals.
abstract: 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.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy. gradoni@iss.it
authors.forename: L
authors.initials: L
authors.lastname: Gradoni
authors.forename: V
authors.initials: V
authors.lastname: Foglia Manzillo
authors.forename: A
authors.initials: A
authors.lastname: Pagano
authors.forename: D
authors.initials: D
authors.lastname: Piantedosi
authors.forename: R
authors.initials: R
authors.lastname: De Luna
authors.forename: M
authors.initials: M
authors.lastname: Gramiccia
authors.forename: A
authors.initials: A
authors.lastname: Scalone
authors.forename: T
authors.initials: T
authors.lastname: Di Muccio
authors.forename: G
authors.initials: G
authors.lastname: Oliva
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D004197:Disease Reservoirs; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007558:Italy; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000473:pathology* / Q000517:prevention & control* / Q000662:veterinary; D008214:Lymphocytes / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D011576:Psychodidae; D011994:Recombinant Proteins / Q000276:immunology; D013987:Ticks; D014611:Vaccination
chemical_list: D000953:Antigens, Protozoan; D018076:DNA, Complementary; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D011994:Recombinant Proteins