Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral "blips".
Antiviral therapy prolongs suppression of viral replication and allows for significant immune reconstitution but has not been effective in eradicating reservoirs of virus, which produce resurgent viremia when highly active antiretroviral therapy (HAART) is discontinued. Immune-based therapy may provide an additional antiviral effect. We vaccinated stable HIV-positive patients on HAART with an HIV plasmid vaccine to determine safety, immunogenicity, and therapeutic potential. Volunteers received a combination of two HIV DNA plasmid constructs, which drive expression of env/rev and gag/pol genes. The vaccine was well tolerated with no toxicity. CD4 and CD8 lymphocyte counts did not change significantly among volunteers. CD8 MHC class I-restricted responses to HIV antigens were assayed. Eight of 13 vaccinees responded after vaccination with detectable ELISpot result. Importantly, we observed a difference in viral detection events in vaccinated compared to control patients. Three out of the five placebo recipients had "viral blips" (transient elevations of HIV RNA) during follow-up (10/49 assays) while these were only present in one of 13 vaccinees on one occasion (1/130 assays; p<0.04). The decrease in the frequency of transient viremia and failure suggests that DNA immunization with CD8-generating vaccines in HAART-controlled HIV-positive subjects may have therapeutic potential.
MacGregor
Rob Roy
RR
Department of Medicine, University of Pennsylvania School of Medicine, 502 Johnson Pavilion, 36th & Hamilton Walk, Philadelphia, PA 19104-6073, USA.
Boyer
Jean D
JD
Ugen
Kenneth E
KE
Tebas
Pablo
P
Higgins
Terry J
TJ
Baine
Yaela
Y
Ciccarelli
Richard B
RB
Ginsberg
Richard S
RS
Weiner
David B
DB
D016915:AIDS Vaccines / Q000235:genetics* / Q000627:therapeutic use*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D012449:Safety; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000628:therapy / Q000821:virology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D012367:RNA, Viral; D019444:Vaccines, DNA