Merck to begin larger trial with adenovirus vector

At the AIDS Vaccine 04 Conference in Lausanne, Switzerland, Merck & Co. announced that it would begin a large-scale trial of its MRK-Ad5 vaccine candidate by the end of this year. The vaccine candidate is an adenovirus type 5 vector (see Primer) that carries some HIV genes from a clade B virus. Vaccine researchers consider this candidate to be one of the most promising. In early clinical trials, the vaccine stimulated a strong cell-mediated immune response to HIV. This will be a Phase II “proof of concept” trial to determine whether one arm of the immune response, cell-mediated immunity, can either prevent HIV infection or lessen disease in vaccinated people who are later exposed to HIV through high-risk behavior.

A limitation of the vaccine candidate is that many people have already been naturally infected with the vector virus, adenovirus type 5. This virus causes a form of the common cold and many people have pre-existing immune responses to it, including antibodies. So people who have a strong antibody response and are given this vaccine candidate may have a decreased immune response to the HIV genes carried by the vector. To avoid this potential problem MRK-Ad5 will be tested in areas where people have low levels of antibodies to the adenovirus type 5 vector.

Researchers are already working to overcome the problem of pre-existing immunity. At Lausanne, Dan Barouch of Harvard Medical School reported on mouse studies using adenovirus types 11 and 35 that carry some simian immunodeficiency virus (SIV) genes. Scientists do not think that these two types of adenovirus will be affected as much by preexisting immunity because types 11 and 35 infect humans less commonly and don’t cause such strong antibody responses. The mice showed strong immune responses to this vaccine candidate.