Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model.
In this study, we investigated the ability of a multigenic SIV DNA prime/replication-defective adenovirus serotype 5 (rAd/SIV) boost regimen to induce SIV-specific immune responses and protection against intrarectal challenge with SIVmac251 in rhesus macaques. Four rhesus macaques were immunized intramuscularly three times at 8-week intervals with SIV DNA vaccine and boosted once with rAd/SIV vaccine Four control macaques received the same amount of mock plasmid DNA and mock adenovirus vector. While the SIV DNA vaccine included plasmids expressing a mutated human IL-12 gene (IL-12N222L) as well as SIVmac239 structural and regulatory genes, the rAd/SIV vaccine contained rAd vectors expressing SIVmac239 genes only. Immunization with SIV DNA vaccine alone induced SIV-specific IFN-gamma ELISPOT responses in only two of four vaccinated macaques, whereas all animals developed SIV-specific T-cell responses and Env- and Tat-specific antibody responses following the rAd/SIV vaccine boost. Upon intrarectal challenge with pathogenic SIVmac251, strong anamnestic Env-specific binding and neutralizing antibody responses were detected in the vaccinated macaques. Overall, the immunized macaques had lower peak and set-point viral loads than control macaques, suggesting that the induced immune responses play a role in the control of viremia. In addition, the loss of CD4+ T cells was delayed in the vaccinated macaques after challenge. These results indicate that the multigenic DNA prime-adenovirus boost immunization may be a promising approach in developing an effective AIDS vaccine.
Suh
You S
YS
Department of Virology and Immunology, German Primate Center, Göttingen, Germany.
Park
Ki S
KS
Sauermann
Ulrike
U
Franz
Monika
M
Norley
Stephen
S
Wilfingseder
Doris
D
Stoiber
Heribert
H
Fagrouch
Zahra
Z
Heeney
Jonathan
J
Hunsmann
Gerhard
G
Stahl-Hennig
Christiane
C
Sung
Young C
YC
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D018791:CD4 Lymphocyte Count; D005822:Genetic Vectors; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology; D008253:Macaca mulatta; D009500:Neutralization Tests; D010957:Plasmids; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D014766:Viremia
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D018664:Interleukin-12; D007371:Interferon-gamma