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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