SEATTLEA new HIV-1 vaccine that uses a replication-defective adenovirus
vector has proved to be safe, well tolerated, and immunogenic to date in an
ongoing phase I trial, according to research presented at the 9th Conference on
Retroviruses and Opportunistic Infections (abstract 12). Emilio Emini, PhD,
senior vice president of vaccine research at Merck Research Laboratories,
presented the results.
"The clinical goals of our vaccine effort are to develop a vaccine that
will lessen the likelihood of persistent virus infection or, should infection
occur, lead to the establishment of a clinically significant lowered virus
load," Dr. Emini said. "The other potential use of these vaccines is
that, in HIV-infected individuals, in combination with HAART, the elicited
immune responses could mitigate the effects of previously established HIV
The Merck vaccine development effort is focusing on the cellular response
(specifically the CD8 and CD4 cellular responses) to HIV-1, because intensive
vaccine efforts to date have not been able to produce a strong, broadly
reactive, virus-neutralizing antibody response, Dr. Emini said.
The development of a vaccine designed specifically to elicit a cellular
immune response is a novel area of research, according to John Shiver, PhD,
senior director and head of viral vaccine research at Merck Research
Laboratories. "There are no other vaccines for other disease targets that
intentionally produce killer lymphocytes against a virus," he said.
In an estimated 5 years of preclinical research at Merck, two HIV-1 vaccines
have emerged as viable candidates and are currently being tested in humans: a
naked DNA vaccine and a replication-defective adenovirus vector vaccine. Both
vaccines carry DNA encoding the HIV-1 gag structural protein with the clade B
gene sequence, Dr. Emini said.
The gag protein was selected after assessing cellular immune responses in
HIV-1 infected individuals in North America, Brazil, Thailand, and Malawi. The
tests showed that the response to HIV-1 is most consistently and most strongly
directed against the gag protein, followed by the pol and nef proteins.
Clade B is one of the three most common clades (genetic variants) of HIV-1
worldwide, although data from the same international population revealed
considerable cross-reactivity of the cellular immune response, Dr. Emini noted.