Engineering of noninfectious HIV-1-like particles containing mutant gp41 glycoproteins as vaccine candidates that allow vaccinees to be distinguishedfrom HIV-1 infectees

Many AIDS vaccine candidates under development may elicit immune responses similar to those observed in and used to screen human immunodeficiency viru s type 1 (HIV-l)-infected individuals. Therefore, it is important to develo p vaccine candidates that incorporate antigenic markers and allow vaccinees to be distinguished from HIV-1 infectees. To this end, we introduced a ser ies of mutations into and in the vicinity of the major immunodominant regio n (MIR) of gp41 (residues 598-609), a domain recognized by almost all HIV-1 infectees, and evaluated whether HIV-l-like particles incorporating such m utant glycoproteins could be expressed in mammalian cells. Results indicate d that although up to three consecutive amino acids could be replaced withi n MIR without significantly affecting particle formation or gp160 processin g, deletions within MIR impaired envelope processing. Replacement of HIV-I MIR by part or most of the corresponding domain from other lentiviruses mar kedly decreased or abolished gp160 processing. Synthetic peptides correspon ding to a mutated MIR incorporating three amino acid replacements were not recognized by a panel of sera from HIV-1 infectees, suggesting that HIV-l-l ike particles with this type of mutation represent potential candidate vacc ines that could allow vaccinees to be distinguished from HIV-I infectees. ( C) 1999 Academic Press.