Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes.
East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8(+) cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8(+) CTL from immune cattle. CD8(+) T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.
International Livestock Research Institute, Nairobi, Kenya.
Simon P
SP
Graham
Roger
R
Pellé
Yoshikazu
Y
Honda
Duncan M
DM
Mwangi
Nyerhovwo J
NJ
Tonukari
Mat
M
Yamage
E Jane
EJ
Glew
Etienne P
EP
de Villiers
Trushar
T
Shah
Richard
R
Bishop
Evelyne
E
Abuya
Elias
E
Awino
James
J
Gachanja
Anthony E
AE
Luyai
Ferdinand
F
Mbwika
Anthony M
AM
Muthiani
David M
DM
Ndegwa
Moses
M
Njahira
John K
JK
Nyanjui
Fredrick O
FO
Onono
Julius
J
Osaso
Rosemary M
RM
Saya
Claude
C
Wildmann
Claire M
CM
Fraser
Ian
I
Maudlin
Malcolm J
MJ
Gardner
Subhash P
SP
Morzaria
Sheena
S
Loosmore
Sarah C
SC
Gilbert
Jean-Christophe
JC
Audonnet
Pierre
P
van der Bruggen
Vishvanath
V
Nene
Evans L N
EL
Taracha
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002417:Cattle; D002460:Cell Line; D016052:Protozoan Vaccines / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016797:Theileria parva / Q000276:immunology*; D013801:Theileriasis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014611:Vaccination
D000953:Antigens, Protozoan; D016052:Protozoan Vaccines