Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis.
Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.
Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Heslington, UK.
Asher
A
Maroof
Najmeeyah
N
Brown
Barbara
B
Smith
Michael R
MR
Hodgkinson
Alice
A
Maxwell
Florian O
FO
Losch
Ulrike
U
Fritz
Peter
P
Walden
Charles N J
CN
Lacey
Deborah F
DF
Smith
Toni
T
Aebischer
Paul M
PM
Kaye
D000256:Adenoviridae; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood; D007893:Leishmania donovani / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000469:parasitology; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; C401884:HASPB protein, Leishmania; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C090009:kinetoplastid membrane protein 11, Leishmania donovani