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151 Role of Poxvirus Vectors in the Development of an HIV Vaccine

Pantaleo, Giuseppe M.D.

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 62
doi: 10.1097/01.qai.0000397336.79987.d8

Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland

Virus vectors together with DNA plasmid vectors have been instrumental for the development of the so-called HIV T-cell vaccines. The development of T-cell vaccines has been based predominantly on two virus vector platforms: a) adenovirus vectors and b) poxvirus vectors. Adenovirus and poxvirus vectors used alone and particularly in combination with plasmid DNA-based vaccines have shown to induce vigorous T-cell responses. Appropriate HIV-specific cellular immunity certainly plays a major direct role in the development of protective immunity and adequate CD4 T-cell help is critical for the development of optimal B-cell/antibody response. The overall concept of T-cell vaccines has been harshly questioned following the failure of a phase IIb study investigating an adenovirus serotype 5 (Ad5)-based HIV vaccine candidate expressing gag-pol-nef HIV-1 proteins from clade B (known as Step trial). The promising protective effect observed in the RV-144 phase III efficacy clinical trial in Thailand which has tested a poxvirus/gp120 combination has indicated the importance of developing immunization strategies capable of stimulating both humoral and cellular arms of the immune response. Although the protective effect was modest, the RV-144 trial has shown that a poxvirus plus protein HIV vaccine combination is able to prevent HIV infection. These results also indicate that both components of the vaccine, i.e. the priming component (ALVAC) and the boosting component (the gp120 protein) need to be improved. With regard to the improvement of the cellular component of the vaccine-induced immune response, a number of novel poxvirus vectors have been developed which have an immunogenicity profile substantially improved compared to ALVAC. These novel vectors in combination with a gp120 protein component are ready to move into large clinical trials. The limited sets of immunological results of the RV-144 trial do not allow to rule out or to favor any specific cellular or humoral mechanism of protection. Additional mechanisms of protection, i.e.innate immunity mechanisms, beyond the conventional CD4 and cytotoxic CD8 T-cell and neutralizing antibody responses may have played an important role. Hopefully, the improved vaccine combinations should aim at eliciting an integrated immune response, i.e. innate, humoral and cellular immunity. Furthermore, highly attenuated replication competent poxvirus vectors with promising immunogenicity and safety profiles are in advanced stage of development. Therefore, there is a large and interesting portfolio of novel poxvirus vectors that will be critical in sustaining the iterative process needed for the development of an effective HIV vaccine.

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