Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Immune responses triggered by HIV/AIDS vaccine candidates, derived from MVA-B, with deletions in several immune regulatory genes

  • J García-Arriaza1,
  • P Arnáez1,
  • CE Gómez1 and
  • M Esteban1
Retrovirology20129(Suppl 2):P302

DOI: 10.1186/1742-4690-9-S2-P302

Published: 13 September 2012


Poxvirus vector Modified Vaccinia Virus Ankara (MVA) expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (termed MVA-B) is a promising HIV/AIDS vaccine candidate, as it was shown in the results obtained from a phase I clinical trial.


To try to improve the immunogenicity elicited by MVA-B we have generated and characterized the innate immune sensing and the in vivo immunogenicity profile of new optimizing MVA-B vaccine candidates, which contains deletions in one, two or three different immunomodulatory vaccinia virus (VACV) genes blocking the same signaling pathway, involved in the induction of type I IFN.


The innate immune signals elicited by these MVA-B deletion mutants in human macrophages showed an up-regulation of the expression of IFN-β and IFN-α/β-inducible genes. A DNA prime/MVA boost immunization protocol in mice revealed that these MVA-B deletion mutants were able to induce strong and polyfunctional HIV-1-specific CD4+ and CD8+ T-cell adaptive and memory immune responses, which were mostly mediated by CD8+ T cells with an effector phenotype. CD4+ T-cell responses were mainly directed against Env in MVA-B and all the MVA-B deletion mutants. However and interestingly, while MVA-B induced preferentially Env- and Gag-specific CD8+ T-cell responses, MVA-B deletion mutants induced more GPN-specific CD8+ T-cell responses. Moreover, an enhanced HIV-1-specific lymphoproliferative response was observed with the MVA-B deletion mutants. Furthermore, MVA-B and MVA-B deletion mutants were also able to induce antibodies against Env.


These findings revealed that deletion in MVA-B of VACV genes that act blocking the same signaling pathway confers an immunological benefit by inducing innate immune responses and increasing the magnitude, quality and durability of the HIV-1-specific T-cell immune responses. Our observations focused the use of highly optimizing MVA-based vectors as more potent HIV-1 vaccines.

Authors’ Affiliations

Centro Nacional de Biotecnología. CSIC


© García-Arriaza et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.