Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination.
A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge.
Gorelick
R J
RJ
AIDS Vaccine program, SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.
Lifson
J D
JD
Yovandich
J L
JL
Rossio
J L
JL
Piatak
M
M
Scarzello
A J
AJ
Knott
W B
WB
Bess
J W
JW
Fisher
B A
BA
Flynn
B M
BM
Henderson
L E
LE
Arthur
L O
LO
Benveniste
R E
RE
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D008254:Macaca nemestrina; D019251:Nucleocapsid / Q000235:genetics* / Q000276:immunology; D012007:Rectum; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D019444:Vaccines, DNA / Q000276:immunology*; D019562:Viral Load; D014771:Virion / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D019444:Vaccines, DNA