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Immunogenic Profiling in Mice of a HIV/AIDS Vaccine Candidate (MVA-B) Expressing Four HIV-1 Antigens and Potentiation by Specific Gene Deletions
被引:71
作者:
Garcia-Arriaza, Juan
[1
]
Luis Najera, Jose
[1
]
Gomez, Carmen E.
[1
]
Sorzano, Carlos Oscar S.
[2
]
Esteban, Mariano
[1
]
机构:
[1] CSIC, Dept Mol & Cellular Biol, Ctr Nacl Biotecnol, Madrid, Spain
[2] CSIC, Biocomp Unit, Ctr Nacl Biotecnol, Madrid, Spain
来源:
PLOS ONE
|
2010年
/
5卷
/
08期
关键词:
T-CELL RESPONSES;
POXVIRUS VECTORS MVA;
VIRUS ANKARA MVA;
IMMUNE-RESPONSES;
CLADE-C;
PRECLINICAL EVALUATION;
DNA PRIME;
NYVAC;
MEMORY;
VIREMIA;
D O I:
10.1371/journal.pone.0012395
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Background: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs) with immunoregulatory function. Methodology/Principal Findings: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R), known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1 beta, respectively (referred as MVA-B Delta A41L/Delta B16R). A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B Delta A41L/Delta B16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B Delta A41L/Delta B16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1specific CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+) T-cell responses, MVA-B Delta A41L/Delta B16R induced more GPN-specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. Conclusions/Significance: These findings revealed that MVA-B and MVA-B Delta A41L/Delta B16R induced in mice robust, polyfunctional and durable T-cell responses to HIV-1 antigens, but the double deletion mutant showed enhanced magnitude and quality of HIV-1 adaptive and memory responses. Our observations are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors as HIV-1 vaccines.
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