Novel Candidate HIV Vaccine Vector Reported
HIV and AIDS Vaccine
Researchers at Beth Israel Deaconess Medical Center (BIDMC) in collaboration with Crucell Holland BV, a Dutch biotechnology company, have created a novel HIV vaccine strategy that overcomes the problem of pre-existing anti-vector immunity, which may prove a limitation of current lead AIDS vaccine candidates. These new findings were reported on April 16, 2006 in the journal Nature.
Lead AIDS vaccine candidates under development utilize adenovirus serotype 5 (Ad5) vectors to transport HIV antigens into cells in order to generate HIV-specific cellular immune responses. Although adenoviruses are known to cause the common cold, Ad5 vaccine vectors have been weakened to make them replication-incompetent and thus safe for use as vaccines.
"A potential limitation of Ad5 vectors is that the majority of individuals, particularly in sub-Saharan Africa, have pre-existing immunity against the Ad5 vector," explains the study's senior author Dan H. Barouch, MD, PhD, a scientist in the Division of Viral Pathogenesis at BIDMC and Assistant Professor of Medicine at Harvard Medical School. Pre-existing antibodies against Ad5 could neutralize Ad5 vaccine vectors before they have a chance to do their job.
"We observed that the majority of Ad5-specific antibodies target the major hexon capsid protein," Barouch explains, adding that the hexon's outer surface consists of loops known as hypervariable regions. "We therefore swapped the hexon surface loops with the corresponding regions from the rare adenovirus serotype Ad48."
The novel chimeric vector retained many desirable features of Ad5 vectors but was not inhibited by pre-existing immunity against Ad5 in both mice and rhesus monkeys. Moreover, the chimeric vector generated strong immune responses against the vaccine antigen: the Gag protein from simian immunodeficiency virus.
AIDS remains one of the world's most devastating health problems, with 4.9 million new infections and 3.1 million deaths worldwide in 2004 alone.
"Although much work remains to be done, we are encouraged by these new findings and plan to explore whether this vector can be developed further into clinical trials as a potentially improved HIV-1 vaccine candidate," says Barouch.