Four New AIDS Vaccine Trials Launched in Recent Weeks
Four new early-stage AIDS vaccine trials were launched in recent weeks. A Phase IIa trial in North and South America and a pair of Phase I trials in the UK and India will test two different prime-boost regimens of DNA and modified vaccinia Ankara (MVA) vector-based vaccine candidates. Another Phase I trial in the US is evaluating the safety and immunogenicity of an adenovirus serotype 35 (Ad35)-based candidate.
The trial furthest along, a Phase IIa trial testing the safety and immunogenicity of two vaccine candidates developed by US-based GeoVax, began enrolling volunteers in January at 13 clinical trial centers in the United States and Peru. The trial known as HVTN 205 will involve 225 volunteers and is being conducted in collaboration with the US National Institutes of Health and the HIV Vaccine Trials Network (HVTN).
Volunteers randomly selected to receive the vaccine candidates in HVTN 205 will receive two doses of a DNA vaccine candidate encoding HIV clade B Gag, Pol, Env, Tat, Rev, and Vpu, followed by two doses of an MVA-based vaccine candidate carrying HIV clade B Gag, Pol, and Env proteins.
Harriet Robinson, senior vice president of research and development at GeoVax, says the vaccine candidates showed “fabulous control” against SHIV, a hybrid HIV/ simian immunodeficiency virus (SIV), 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.
In December 2008, IAVI in conjunction with St. Stephen’s AIDS Trust at the Chelsea and Westminster Hospital in London initiated a Phase I clinical trial involving 32 volunteers to evaluate the safety and immunogenicity of a different DNA/MVA prime-boost regimen. This regimen involves the candidate TBC-M4, which utilizes an MVA vector to deliver clade C HIV env,gag, rev, reverse transcriptase, tat, and nef genes. TBC-M4 was developed in collaboration with the National Institute of Cholera and Enteric Diseases in India and was tested previously in a Phase I trial conducted there.
In the Phase I trial in the UK, administration of TBC-M4 will be preceded by a DNA-based vaccine candidate called ADVAX, a plasmid DNA candidate encoding HIV clade C env, gag, pol, nef, and tat genes. ADVAX 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 syringe injection.
In this trial investigators will evaluate blood samples from the volunteers using a viral suppression assay to determine whether the CD8+ T cells produced in response to the TBC-M4/ADVAX vaccine candidates are capable of inhibiting HIV. “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.
Since ELISPOT results are not necessarily an accurate predictor of whether a vaccine can prevent or control HIV infection, Gilmour says it’s important to find other tests, such as the viral suppression assay, that could potentially provide better insights into the immunogenicity of vaccine candidates. The viral suppression assay being used in the UK trial is an optimized version of one developed by Bruce Walker, director of the Ragon Institute in Boston (see $100 million Gift Creates New AIDS Vaccine Research Institute).
Another Phase I, prime-boost trial of TBC-M4/ADVAX in India, known as P001, was also recently announced by the Indian Council of Medical Research. This trial will enroll volunteers at sites in Pune and Chennai and will evaluate different doses and vaccination regimens of the two candidates. In the UK trial, volunteers randomized to receive the vaccine candidates will either receive two doses of ADVAX via Biojector followed by an injection of TBC-M4, or three injections of TBC-M4. Volunteers will be followed for six months after receiving their last vaccination. In the India trial, volunteers will receive either two doses of ADVAX by traditional syringe injection followed by two injections of TBC-M4, or three injections of TBC-M4.
IAVI is also planning to begin enrollment of volunteers in a Phase I trial of its Ad35-based vaccine candidate encoding the GRIN insert (HIV clade A Gag, Pol [RT and Int], and Nef), as well as HIV clade A Env. This candidate was manufactured by the French biotechnology company Transgene. The trial will enroll 42 volunteers at New York State’s University of Rochester Medical Center who will receive either two intramuscular injections of the vaccine candidate or placebo at three different doses. Clinicians will first administer the lowest dose and will review the safety data before proceeding to the next higher dose. —Regina McEnery