The US National Institute of Allergy and Infectious Diseases (NIAID) announced on Thursday that it will not move ahead with the PAVE 100 study, which was intended to test a vaccine with similarities to the failed Merck Ad5-vectored HIV vaccine.
PAVE was originally intended to recruit 8500 volunteers in the United States, South America, the Caribbean and Eastern and Southern Africa. The study was to begin US recruitment in October 2007 but was postponed in October 2007 following the decision to halt immunisations in the STEP HIV vaccine study due to the failure of the Merck vaccine used in that study to protect against HIV infection.
That study also raised concerns about the use of an adenoviral vector (the carrier for the HIV gene sequences delivered in the vaccine) due to the finding that men who were both uncircumcised and had pre-existing neutralising antibodies to adenovirus type 5 (Ad5) had the highest risk of HIV infection during the study.
PAVE was designed to study a different vaccine product, called VRC, which consisted of a DNA-based plasmid vaccine and a follow-up booster vaccine that used an adenovirus (a common cold virus) as a vector to deliver recombinant HIV sequences from a variety of HIV sub-types.
However, there was little scientific confidence that the PAVE 100 study would lead on directly to licensing of the VRC vaccine. Instead, the study would at best have provided further information to the field about immune responses to so-called T-cell vaccines, which stimulate T-lymphocyte responses to HIV, and about the safety of an adenoviral vector.
Nevertheless, an advisory group recommended in May that a smaller version of PAVE 100 should go ahead.
But NIAID decided that a large-scale study of the VRC vaccine was not warranted, and in press interviews yesterday NIAID director Dr Tony Fauci told reporters that his agency wanted to see if the vaccine reduced viral load in people who became infected despite vaccination, as a first step towards proving that the concept of a T-cell based vaccine is workable. In the STEP study of the Merck vaccine, vaccination had no effect on viral load levels in people who became infected during the study.
Vaccine advocates agree that the decision should not be seen as a vote of no confidence in the overall search for an HIV vaccine.
“In deciding not to go ahead with PAVE 100, Dr. Fauci and NIAID have likely considered other fiscal and feasibility considerations beyond these scientific recommendations,” said AIDS Vaccine Advocacy Coalition Executive Director Mitchell Warren. “The reality of science is that these issues also carry great weight. However, after nearly a year of public hand-wringing and unproductive public attacks on the entire search for an AIDS vaccine, it is essential that this decision not be viewed as a vote of noconfidence for the overall endeavour.”
International AIDS Vaccine Initiative President and CEO Seth Berkley said: "The NIAID decision is a bold decision that bears in mind the lessons offered by the STEP study. That is the way good scientific endeavours work. The decision by NIAID does not reflect paralysis in the AIDS vaccine field, or a lack of direction forward. In fact, it reflects the opposite. It reflects the dynamic learning that is the scientific process, that is pharmaceutical product development.”