Vaccination against drug resistance in HIV infection

Abstract

HIV-1 resistance to currently employed antiretroviral drugs and drug-associated adverse reactions and toxicity point to a need for additional measures to control HIV-1 replication in HIV-infected patients. The immune system of HIV-infected individuals mount an immune response against the regions harboring drug-resistance mutations, sometimes stronger than that against the parental wild-type sequences. A potent cross-reactive immune response against drug-resistant pol proteins can suppress the replication of drug-escaping HIV. This suggests the possibilty for a vaccination against existing and anticipated drug-resistant HIV variants. If successful, therapeutic vaccines against drug resistance would ease the therapeutic modalities and limit the spread of drug-resistant HIV. A better understanding of the complex interactions between patterns of drug-resistance mutations, immune responses against these mutations and their antigen presentation by particular human lymphocyte antigen alleles could help to tailor these vaccines after new drugs/new mutations. In this review, we describe the developments in the field of immunization against mutations conferring drug resistance and evaluate their prospects for human vaccination.

Keywords::

• antigen retargeting
• cytotoxic T lymphocyte
• DNA vaccine
• drug resistance
• epitope
• highly active antiretroviral therapy
• HIV-1
• human lymphocyte antigen binding
• immune hierarchy
• immunity to mutations
• immunogen design
• processing
• therapeutic vaccination

Acknowledgements

The authors would like to express sincere gratitude to Britta Wahren and Göran Bratt for many helpful discussions during writing of the manuscript.

Financial & competing interests disclosure

This work has been carried out in the frame of HIVIS project, EudraCT 2004-002876-40. EU projects AVIP LSHP-CT-2004-503487, and Europrise LSHP-CT-2006-037611 are acknowledged for financial support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.