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Two Prime-Boost Regimens Enter Clinical Trials

GeoVax Launches Phase IIa Trial

A Phase IIa trial testing the safety and immunogenicity of a prime-boost regimen of two vaccine candidates developed by US-based GeoVax is now enrolling volunteers in the US and Peru. This trial, known as HVTN 205, launched on December 1, World AIDS Day, and will involve 225 volunteers.

Those randomly selected to receive the vaccine candidates will receive a prime-boost regimen of two doses of a DNA candidate carrying three HIV fragments or immunogens, followed by two doses of a modified vaccinia Ankara (MVA) virus vector carrying the same immunogens. The MVA vector cannot cause disease, and neither of the vaccine candidates can cause HIV infection.

Harriet Robinson, vice president of research and development at GeoVax, says the vaccine candidates showed "fabulous control" of infection with a hybrid virus that combines parts of HIV and simian immunodeficiency virus (SIV), the monkey equivalent of HIV, in preclinical studies in non-human primates. The candidates did not fare as well against SIV challenge but still showed a 10-fold reduction in viral load after six months compared to unvaccinated control animals, says Robinson.

Vaccinations Begin in IAVI's Phase I Trial

IAVI, in conjunction with St. Stephen's AIDS Trust and Chelsea-Westminster Hospital in the UK, has launched a Phase I clinical trial involving 32 volunteers in London to evaluate the safety and immune responses induced by two AIDS vaccine candidates administered in a prime-boost regimen.

One of these candidates, called TBC-M4, utilizes an MVA vector to deliver non-infectious HIV fragments in the hope of inducing an immune response against HIV. This candidate, developed in collaboration with the National Institute of Cholera and Enteric Diseases in India, was tested previously in a Phase I trial conducted in Chennai, India. In this new trial, administration of TBC-M4 will be preceded by a DNA-based vaccine candidate called ADVAX, which was developed at the Aaron Diamond AIDS Research Center in New York City in collaboration with Rockefeller University and IAVI. The ADVAX vaccinations will be administered with a needle-free device called Biojector 2000 to see if this delivery system induces stronger immune responses than a regular syringe injection.

This UK trial will also allow researchers to assess the merits of a new laboratory test known as a viral suppression assay to determine whether the CD8+ T cells, produced in response to the vaccine candidates, that are isolated from volunteers in the vaccine trial are capable of inhibiting HIV in the lab. "What we would like to do is see if the CD8+ T cells after vaccination stop the virus from growing," says Jill Gilmour, senior director of clinical research at IAVI.

The assay being used in this trial is an optimized version of one developed by Bruce Walker, director of the Partners AIDS Research Center at Massachusetts General Hospital, who has long advocated for researchers to use this type of assay to measure the function of immune cells produced in response to vaccination. Most often the immune responses induced by candidate vaccines in clinical trials are assessed using an ELISPOT assay. This assay detects the number of CD8+ T cells that are excreting specific proteins known as cytokines but does not measure the ability of these cells to actually inhibit HIV (see VAX August 2007 Primer on Understanding Immunogenicity). —By Regina McEnery