Novel vaccine delivery systems: solutions to HIV vaccine dilemmas?

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The history of successful vaccination against severe viral diseases such as smallpox poliomyelitis or measles led to the initial hope that a vaccine against AIDS would be developed quickly. However an effective vaccine against HIV needs to overcome substantial obstacles that emerged as research progressed. Due to life cycle HIV can effectively hide from the host immune response integrating itself as proviral DNA in the host cell genome. A strategy pursued to deal with this difficulty is to include early viral regulatory proteins such as Tat Rev or Nef as vaccine antigens for induction of immune responses that can recognize and destroy HIV-infected cells as soon as the virus life cycle is activated [12]. The virus preferentially targets and destroys host immune cells such as T-helper lymphocytes macrophages and dendritic cells that are probably essential to maintain an effective antiviral immune response. This would imply that vaccine-elicited immunity unlikely to be able to prevent infection itself must be able to quickly control virus replication to prevent harm to the immune system. The high antigenic variability of HIV can be considered as an extremely effective immune-evasion strategy. Because of the low fidelity of the viral RNA polymerase virus progeny always represents a collection of RNA genomes (quasi-species) with random mutations. In vivo selection of immunodeficiency virus variants that can evade the recognition of neutralizing antibodies is common and strong virus-specific cytotoxic T-cell responses can select for escape variants already during resolution of primary viremia [3]. Most HIV infections are acquired sexually via the genital or rectal mucosae; however at these entry sites it appears difficult to induce strong antiviral immunity by vaccination. Finally HIV infection is a poverty-related disease that is particularly threatening health in societies of the developing world. Therefore vaccine candidates must be safe and feasible in production and administration to be eligible for use where most needed. (excerpt)