Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine.
CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naïve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naïve humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.
Wang
R
R
Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Doolan
D L
DL
Le
T P
TP
Hedstrom
R C
RC
Coonan
K M
KM
Charoenvit
Y
Y
Jones
T R
TR
Hobart
P
P
Margalith
M
M
Ng
J
J
Weiss
W R
WR
Sedegah
M
M
de Taisne
C
C
Norman
J A
JA
Hoffman
S L
SL
D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007115:Immunization Schedule; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000953:Antigens, Protozoan; D006680:HLA Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan