Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia

被引:63
作者
Pinder, M
Reece, WHH
Plebanski, M
Akinwunmi, P
Flanagan, KL
Lee, EAM
Doherty, T
Milligan, P
Jaye, A
Tornieporth, N
Ballou, R
Mcadam, KPMJ
Cohen, J
Hill, AVS
机构
[1] MRC Labs, Banjul, Gambia
[2] Glaxo SmithKline Biol, Rixensart, Belgium
[3] John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England
[4] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA
[5] Austin Res Inst, Vaccine Dev & Infect Dis Unit, Melbourne, Vic, Australia
关键词
cell-mediated immunity; circumsporozoite; ELISPOT; Plasmodium falciparum; vaccine;
D O I
10.1111/j.1365-2249.2004.02371.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field.
引用
收藏
页码:286 / 293
页数:8
相关论文
共 21 条
[1]   Efficacy of RTS,S/ASO2 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia:: a randomised trial [J].
Bojang, KA ;
Milligan, PJM ;
Pinder, M ;
Vigneron, L ;
Alloueche, A ;
Kester, KE ;
Ballou, WR ;
Conway, DJ ;
Reece, WHH ;
Gothard, P ;
Yamuah, L ;
Delchambre, M ;
Voss, G ;
Greenwood, BM ;
Hill, A ;
McAdam, KPWJ ;
Tornieporth, N ;
Cohen, JD ;
Doherty, T .
LANCET, 2001, 358 (9297) :1927-1934
[2]   Phototyping: Comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP) [J].
Bunce, M ;
ONeill, CM ;
Barnardo, MCNM ;
Krausa, P ;
Browning, MJ ;
Morris, PJ ;
Welsh, KI .
TISSUE ANTIGENS, 1995, 46 (05) :355-367
[3]   A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in the Gambia [J].
Doherty, JF ;
Pinder, M ;
Tornieporth, N ;
Carton, C ;
Vigneron, L ;
Milligan, P ;
Ballou, WR ;
Holland, CA ;
Kester, KE ;
Voss, G ;
Momin, P ;
Greenwood, BM ;
McAdam, KPWJ ;
Cohen, J .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1999, 61 (06) :865-868
[4]   EVIDENCE OF ENDOTHELIAL INFLAMMATION, T-CELL ACTIVATION, AND T-CELL REALLOCATION IN UNCOMPLICATED PLASMODIUM-FALCIPARUM MALARIA [J].
ELHASSAN, IM ;
HVIID, L ;
SATTI, G ;
AKERSTROM, B ;
JAKOBSEN, PH ;
JENSEN, JB ;
THEANDER, TG .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1994, 51 (03) :372-379
[5]   Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays [J].
Flanagan, KL ;
Lee, EAM ;
Gravenor, MB ;
Reece, WHH ;
Urban, BC ;
Doherty, T ;
Bojang, KA ;
Pinder, M ;
Hill, AVS ;
Plebanski, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (08) :4729-4737
[6]   Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4+ T cells [J].
Geginat, J ;
Sallusto, F ;
Lanzavecchia, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (12) :1711-1719
[7]   HUMAN T-CELL RECOGNITION OF THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - IMMUNODOMINANT T-CELL DOMAINS MAP TO THE POLYMORPHIC REGIONS OF THE MOLECULE [J].
GOOD, MF ;
POMBO, D ;
QUAKYI, IA ;
RILEY, EM ;
HOUGHTEN, RA ;
MENON, A ;
ALLING, DW ;
BERZOFSKY, JA ;
MILLER, LH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (04) :1199-1203
[8]   SAFETY, IMMUNOGENICITY, AND EFFICACY OF A RECOMBINANTLY PRODUCED PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE-PROTEIN HEPATITIS-B SURFACE-ANTIGEN SUBUNIT VACCINE [J].
GORDON, DM ;
MCGOVERN, TW ;
KRZYCH, U ;
COHEN, JC ;
SCHNEIDER, I ;
LACHANCE, R ;
HEPPNER, DG ;
YUAN, G ;
HOLLINGDALE, M ;
SLAOUI, M ;
HAUSER, P ;
VOET, P ;
SADOFF, JC ;
BALLOU, WR .
JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (06) :1576-1585
[9]   Cellular changes and apoptosis in the spleens and peripheral blood of mice infected with blood-stage Plasmodium chabaudi chabaudi AS [J].
Helmby, H ;
Jönsson, G ;
Troye-Blomberg, M .
INFECTION AND IMMUNITY, 2000, 68 (03) :1485-1490
[10]  
Hoffman Stephen L., 1996, P35