Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine.
An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.
Fuller
Deborah Heydenburg
DH
PowderJect Vaccines, Inc., Madison, Wisconsin 53711, USA.
Rajakumar
Premeela A
PA
Wilson
Lawrence A
LA
Trichel
Anita M
AM
Fuller
James T
JT
Shipley
Tim
T
Wu
Mary S
MS
Weis
Kathleen
K
Rinaldo
Charles R
CR
Haynes
Joel R
JR
Murphey-Corb
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D015686:Gene Products, env / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007422:Intestines / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D012007:Rectum / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage*; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage; D014759:Viral Envelope Proteins
D000914:Antibodies, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus