Modular multiantigen T cell epitope-enriched DNA vaccine against human leishmaniasis.
The leishmaniases are protozoal diseases that severely affect large populations in tropical and subtropical regions. There are only limited treatment options and preventative measures. Vaccines will be important for prevention, control and elimination of leishmaniasis, and could reduce the transmission and burden of disease in endemic populations. We report the development of a DNA vaccine against leishmaniasis that induced T cell-based immunity and is a candidate for clinical trials. The vaccine antigens were selected as conserved in various Leishmania species, different endemic regions, and over time. They were tested with T cells from individuals cured of leishmaniasis, and shown to be immunogenic and to induce CD4(+) and CD8(+) T cell responses in genetically diverse human populations of different endemic regions. The vaccine proved protective in a rodent model of infection. Thus, the immunogenicity of candidate vaccine antigens in human populations of endemic regions, as well as proof of principle for induction of specific immune responses and protection against Leishmania infection in mice, provides a viable strategy for T cell vaccine development.
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology (Council of Scientific and Industrial Research), 4 Raja S.C. Mullick Road, Kolkata 700032, India.
Shantanabha
S
Das
Anja
A
Freier
Thouraya
T
Boussoffara
Sushmita
S
Das
Detlef
D
Oswald
Florian O
FO
Losch
Melanie
M
Selka
Nina
N
Sacerdoti-Sierra
Gabriele
G
Schönian
Karl-Heinz
KH
Wiesmüller
Karin
K
Seifert
Matthias
M
Schroff
Christiane
C
Juhls
Charles L
CL
Jaffe
Syamal
S
Roy
Pradeep
P
Das
Hechmi
H
Louzir
Simon L
SL
Croft
Farrokh
F
Modabber
Peter
P
Walden
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007896:Leishmaniasis / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use*
D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D019444:Vaccines, DNA