Nucleic acids encoding self-assembled, non-infectious, non-repli

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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435236, 4351723, 435 914, 4241881, 4241991, 4242081, C07H 2104

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active

059123389

ABSTRACT:
This invention is directed toward nucleic acids encoding self-assembled, non-infectious, non-replicating, immunogenic retrovirus-like particles comprising modified HIV-1 genomes devoid of long terminal repeats and containing nucleotide sequences encoding chimeric envelope glycoproteins. Retrovirus-like particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. One preferred embodiment discloses the engineering of a series of expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1.sub.LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. Immunization with HIV-like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1.sub.LAI and HIV-1.sub.MN isolates.

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