Induction in humans of CD8+ and CD4+ T cell and antibody responses by sequential immunization with malaria DNA and recombinant protein.
Vaccine-induced protection against diseases like malaria, AIDS, and cancer may require induction of Ag-specific CD8(+) and CD4(+) T cell and Ab responses in the same individual. In humans, a recombinant Plasmodium falciparum circumsporozoite protein (PfCSP) candidate vaccine, RTS,S/adjuvant system number 2A (AS02A), induces T cells and Abs, but no measurable CD8(+) T cells by CTL or short-term (ex vivo) IFN-gamma ELISPOT assays, and partial short-term protection. P. falciparum DNA vaccines elicit CD8(+) T cells by these assays, but no protection. We report that sequential immunization with a PfCSP DNA vaccine and RTS,S/AS02A induced PfCSP-specific Abs and Th1 CD4(+) T cells, and CD8(+) cytotoxic and Tc1 T cells. Depending upon the immunization regime, CD4(+) T cells were involved in both the induction and production phases of PfCSP-specific IFN-gamma responses, whereas, CD8(+) T cells were involved only in the production phase. IFN-gamma mRNA up-regulation was detected in both CD45RA(-) (CD45RO(+)) and CD45RA(+)CD4(+) and CD8(+) T cell populations after stimulation with PfCSP peptides. This finding suggests CD45RA(+) cells function as effector T cells. The induction in humans of the three primary Ag-specific adaptive immune responses establishes a strategy for developing immunization regimens against diseases in desperate need of vaccines.
Wang
Ruobing
R
Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Epstein
Judith
J
Charoenvit
Yupin
Y
Baraceros
Fe Maria
FM
Rahardjo
Nancy
N
Gay
Tanya
T
Banania
Jo-Glenna
JG
Chattopadhyay
Rana
R
de la Vega
Patricia
P
Richie
Thomas L
TL
Tornieporth
Nadia
N
Doolan
Denise L
DL
Kester
Kent E
KE
Heppner
D Gray
DG
Norman
Jon
J
Carucci
Daniel J
DJ
Cohen
Joe D
JD
Hoffman
Stephen L
SL
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma