The US Food and Drug Administration (FDA) may not license for use in the US an AIDS vaccine now in large-scale trials in Thailand because it has “a relatively low level of efficacy,” the agency says. But despite controversy surrounding the vaccine, the FDA continues to support the trials in Thailand.
The Thai health ministry and the US Army launched the trial in October 2003 amid strong criticism from leading HIV researchers, who described the scientific rationale for the $119 million project as “extremely weak” (Science 303, 316; 2004).
The vaccine is a combination of Aventis Pasteur's canary pox vector (ALVAC) and VaxGen's controversial AIDSVAX vaccine. ALVAC stimulates the production of cytotoxic T lymphocytes, the 'killer cells' that destroy HIV-infected cells, and the booster AIDSVAX is intended to stimulate the production of neutralizing antibodies that prevent new cell infection. The combination is primarily designed to protect against clade E of the virus, predominant in Thailand, but also contains a few genes from clade B, which circulates in the US and Europe.
The vaccine is unlikely to work, as the immunological responses so far “have not been impressive,” and the data has been “overstated,” says David Markovitz, an HIV researcher at the University of Michigan.
Critics note that neither component has had much success. In phase 2 trials, the ALVAC component stimulated cytotoxic T lymphocytes in 23% of patients over the course of the trial and only 5–8% at a single time frame. Researchers also tested cell cultures, which are easier to neutralize than clinical isolates, Markovitz says.
In its phase 3 trials, AIDSVAX did not stimulate detectable levels of neutralizing antibodies and had no effect on the viral loads of more than 8,000 volunteers in the US and Thailand. Adding the two components is “like hoping zero plus zero gives you more than zero,” says David Ho, director of the Aaron Diamond AIDS Research Center in New York.
[The two-component vaccine is] like hoping zero plus zero gives you more than zero. David Ho, Aaron Diamond AIDS Research Center in New York.
Despite the low efficacy, UNAIDS officials in Bangkok are confident the vaccine will benefit the Thai population.
The FDA concluded after the September meeting that although the vaccine might be ineffective in the US, “it could have beneficial impact in Thailand.” The trial has been presented as a 'proof-of-concept' study to provide correlates of immune protection and a safety profile for vaccination. But with 16,000 volunteers, the trial is well over the average 1,500–3,000 volunteers for a proof-of-concept study.
In Thailand, trial organizers have been able to recruit fewer than 6,000 volunteers. Experts caution that the trial exploits the volunteers' goodwill and runs the risk of further damaging public confidence in AIDS vaccine trials, experts say. “It is hard to understand why they decided to go ahead with the trial,” says Markovitz.
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Padma, T. Despite snags and skepticism, Thai vaccine trial lumbers on. Nat Med 10, 1267 (2004). https://doi.org/10.1038/nm1204-1267b