Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model

Autor: You S. Suh, Stephen Norley, Zahra Fagrouch, Monika Franz, Gerhard Hunsmann, Ki Seok Park, Young Chul Sung, Jonathan L. Heeney, Ulrike Sauermann, Christiane Stahl-Hennig, Doris Wilfingseder, Heribert Stoiber
Rok vydání: 2005
Předmět:
viruses
animal diseases
T-Lymphocytes
Genetic Vectors
Immunization
Secondary
Simian Acquired Immunodeficiency Syndrome
Viral Nonstructural Proteins
medicine.disease_cause
Antibodies
Viral
Macaque
Injections
Intramuscular
DNA vaccination
Viral vector
Adenoviridae
Interferon-gamma
Adjuvants
Immunologic
Neutralization Tests
biology.animal
medicine
Vaccines
DNA
Animals
Viremia
Neutralizing antibody
Viral Structural Proteins
General Veterinary
General Immunology and Microbiology
biology
ELISPOT
Vaccination
Public Health
Environmental and Occupational Health
SAIDS Vaccines
virus diseases
Simian immunodeficiency virus
Viral Load
biology.organism_classification
Virology
Interleukin-12
Macaca mulatta
CD4 Lymphocyte Count
Infectious Diseases
Lentivirus
Immunology
biology.protein
Molecular Medicine
Simian Immunodeficiency Virus
Plasmids
Zdroj: Vaccine. 24(11)
ISSN: 0264-410X
Popis: 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-γ 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.
Databáze: OpenAIRE
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