Box 1. Focusing on vaccines rather than therapies

In contrast to recent successes with HIV therapeutics, the development of a prophylactic HIV vaccine has proven challenging. After years of HIV research, investigators have identified specific immune responses that they believe to be important in fighting HIV. In particular, research points to a role for CD8⁺ T lymphocytes in the suppression of viral replication and in the control of HIV infection. This is supported by studies showing that CD8⁺ T-lymphocyte responses correlate with HIV resistance in some patients. Vaccines that maximize HIV-specific CD8⁺ T-cell responses have entered clinical development; however, designing a vaccine that prevents HIV infection continues to prove challenging.

A major blow to the community came on September 21, when an independent Data Safety Monitoring Board recommended discontinuation of a phase 2 clinical trial of Merck's V520 HIV vaccine (a trivalent vaccine of gag, pol and nef) after interim analysis showed that the vaccine would not likely prevent HIV infection or reduce viral load. As a result, the approaches of two biotech companies, Vical (San Diego, CA, USA) and GenVec (Gaitherburg, MD, USA), are gaining investor attention.

The Vaccine Research Center at the National Institutes of Health (NIH) is advancing a 'prime/boost' vaccine that incorporates the plasmid DNA technology of Vical to prime the immune system and the adenoviral vector technology of GenVec for an immune booster step. Both the prime and boost portions of the vaccine deliver genes encoding three HIV proteins (gag, pol and env), whereas the DNA prime also incorporates the gene encoding the viral nef protein. Encouraging results from a series of phase 2a clinical trials showed that the DNA prime/adenoviral boost vaccine induces T-cell immune responses in up to 70% of subjects.

Fueling hopes that the NIH's vaccine will be more effective than Merck's V520, the NIH vaccine (i) incorporates a fourth protein (env) known to be important in HIV infection, (ii) includes env genes from all three major HIV subtypes and (iii) uses a heterologous DNA prime/adenoviral boost combination that enables multiple priming and produces both strong CD4⁺ and CD8⁺ T-lymphocyte immune responses.

In the field of HCV vaccines, there is also progress. One example is Intercell's (Vienna) IC41—five synthetic peptides from different regions of the HCV polypeptide containing three T-cell epitopes and the company's proprietary poly-L-arginine–based TLR adjuvant. Investors took note of the company's recent encouraging phase 2 interim results (released in August) showing that IC41 produced a small and sustained, statistically significant reduction in viral load. Final results are expected early next year.