Modified AIDS Vaccine Shows Heightened Immunity in Mice
VaxGen's protein subunit vaccine AIDSVAX is the only AIDS vaccine to enter phase III trials. But even as researchers await the trial results expected this year, many have already turned their attention to other strategies, believing that AIDSVAX is not optimally immunogenic. Taking a different tack, Lawrence Paoletti, HMS assistant professor of medicine at Brigham & Women's Hospital, has looked for ways to improve the existing vaccine.
Paoletti applied a strategy used to create conjugate vaccines for group B Streptococcus. By covalently coupling the capsular polysaccharide (CPS) antigen of group B Streptococcus to an immuogenic protein carrier like tetanus toxoid, the antibody response to CPS dramatically improves.
As reported in the Dec. 1 Journal of Infectious Diseases, Paoletti, working with Ronald Kennedy, professor and chair of microbiology and immunology at Texas Tech University Health Sciences Center, created a similar conjugate vaccine for HIV-1 by coupling the HIV envelope protein gp120 and tetanus toxoid to CPS. They also devised vaccines using the nonglycosylated form of gp120, env2-3, as well as one that carried both proteins.
The vaccines were then tested in a mouse strain known to respond poorly to gp120 alone. The conjugate vaccines all boosted levels of gp120-specific immunoglobulin G. The combined gp120/env2-3 conjugate vaccine performed best, raising levels nearly 100-fold. Serum taken from the mice neutralized both lab-adapted and primary HIV-1 isolates in vitro.
Though the method has yet to demonstrate effectiveness against HIV infection in vivo, Paoletti pointed out that it would be no great leap to carry this vaccine strategy into clinical trials, unlike more untested approaches. All of the individual pieces of this vaccine have been through at least phase II clinical trials, and the conjugation method is also well tested.
Courtney Humphries, Harvard Focus, December 13, 2002