HIV Vaccine Draws Renewed Interest

Studies will look to improve on ‘modest’ benefit of first successful drug.

Almost 7 years after the first evidence that an HIV vaccine is possible, researchers are launching a new trial hoping to improve on the 2009 results.

The vaccine used in the so-called RV-144 trial, conducted in Thailand, yielded modest protection — a reduction in the risk of HIV of about 31%. But it was enough to suggest that tweaking the vaccine might get a better outcome.

“We’re looking for ways — not just of repeating the trial — but of doing better,” commented Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases.
Dieffenbach, whose institute is deeply involved in HIV vaccine research, moderated a press briefing at the International AIDS Conference here where details of the new studies were given.
The RV-144 trial actually used two vaccines — a canarypox virus called ALVAC, engineered so it could not cause disease, and carrying the gag, env, and pro IUV genes. Volunteers were given four injections of ALVAC over 6 months or a matching placebo.
And at the last two injections, volunteers also got a shot of AIDSVAX B/E (which targets the HIV gp120 protein) or placebo — a vaccine candidate that had been tested on its own and found to be safe, but without benefit.
For the current studies, researchers first had to adjust vaccines to target proteins from clade C HIV, which is the type of virus that circulates in Africa, according to Linda-Gail Bekker, MBChB, PhD, of the Desmond Tutu HIV Centre in Cape Town, South Africa. The RV-144 vaccine was aimed at clades B and E, seen in Southeast Asia and elsewhere.

But they also added a new adjuvant to increase its immunogenicity and an extra booster shot at 12 months to the 6-month series of vaccinations used in Thailand, said Bekker, who is also president-elect of the International AIDS Society.
The tweaked vaccine has now been tested for safety and immunogenicity and been given the go-ahead for a full-scale efficacy trial in South Africa, Bekker told reporters.
To get the go-ahead, it had to pass four immunological criteria to show it would work better than RV-144, she said. In a phase II study dubbed HVTN 100 with 250 HIV-negative volunteers, she said, the vaccine candidate showed:
A high antibody response rate to the HIV env protein.
An env antibody response whose magnitude was at least as good as that seen in the RV-144 trial.
A powerful CD4-positive T cell response to env.
And an antibody response to the conserved region between the env V1 and V2 loops.
The vaccine candidate beat pre-specified levels for the go-ahead and also did markedly better than the RV-144 vaccine on all four, Bekker said.
The efficacy trial, HVTN 702, is set to start enrolling 5,400 people across South Africa, with the hope of showing at least a 50% vaccine efficacy, according to Glenda Gray, MBChB, president of the South African Medical Research Council, who will lead the trial.
Results should be available in 2020, she told MedPage Today.
While a 50% efficacy might seem small, Gray said, it’s likely enough to have an important effect on the HIV pandemic in places where there is a high burden of HIV. And it would only be the first step in an “iterative process” that she and others hope would lead eventually to even better vaccines.
And 50% is better than some versions of the annual influenza virus, commented Larry Corey, MD, of the Fred Hutchinson Cancer Research Center in Seattle, and principal investigator of the HIV Vaccine Trials Network, which is sponsoring the new studies.
An HIV vaccine had long been a mirage, Corey noted. At the 2000 AIDS conference here, “there was no mention of it,” he said.
Since then, the emphasis has been on improving treatment, spurred by the realization that HIV therapy is a powerful prevention tool as well as a life-saving intervention. But Corey said the world needs prevention tools “that are so generalizable that can be given to everyone.”
“The best way to do that is a vaccine,” he said.
Gray noted that a vaccine would also fill another need — prevention methods that can be controlled by women, who are often unable to insist their partners use such things as condoms.
“A vaccine is the ultimate female prevention tool,” she said. “You put it in your arm and it works in your vagina.”
While South Africa is gearing up for a trial of a fairly traditional vaccine, investigators are also looking a novel approach — using monoclonal antibodies against HIV to see if they can prevent transmission.
Corey said a study of the “broadly neutralizing antibody” VRC01 started in March in the U.S., South America, and Europe, aiming to see if it reduces the risk of HIV among a cohort of 2,700 men who have sex with men and transgendered women.

And a parallel study began in June in South Africa, aiming at enrolling 1,500 heterosexual women in seven sub-Saharan countries.
The so-called AMP trials, Corey said, are expected to have results by 2018.

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