In vivo protective anti-HIV immune responses in non-human primates through DNA immunization.
An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this context DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. Our group has developed the use of nucleic acid immunization as a possible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized with DNA vectors that express the envelope proteins from HIV-1 contain antibodies specific to the HIV-1 envelope. These sera also neutralize HIV-1 infection in vitro and inhibit cell to cell infection in tissue culture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expressing target cells were observed. In addition, evidence that DNA vaccines are capable of inducing a protective response against live virus was demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus macaques and viral load was lower in the vaccinated group of animals versus the control group of animals. These data encouraged us to analyze this vaccination technique in chimpanzees, the most closely related animal species to man. We observed the induction of both cellular and humoral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
J D
JD
Boyer
B
B
Wang
K E
KE
Ugen
M
M
Agadjanyan
A
A
Javadian
P
P
Frost
K
K
Dang
R A
RA
Carrano
R
R
Ciccarelli
L
L
Coney
W V
WV
Williams
D B
DB
Weiner
D016915:AIDS Vaccines; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D000917:Antibody Formation; D004279:DNA, Viral / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000096:biosynthesis / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D018482:Muscle, Skeletal / Q000473:pathology; D002679:Pan troglodytes; D010957:Plasmids / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160