Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine.
We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.
Wang
R
R
Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Epstein
J
J
Baraceros
F M
FM
Gorak
E J
EJ
Charoenvit
Y
Y
Carucci
D J
DJ
Hedstrom
R C
RC
Rahardjo
N
N
Gay
T
T
Hobart
P
P
Stout
R
R
Jones
T R
TR
Richie
T L
TL
Parker
S E
SE
Doolan
D L
DL
Norman
J
J
Hoffman
S L
SL
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016054:DNA, Protozoan / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma