Nucleic acids encoding self-assembled, non-infectious, non-replicating, immunogenic retrovirus-like particles comprising modified HIV genomes and chimeric envelope glycoproteins
US5912338A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | May 30, 1995 |
| Grant date | Jun 15, 1999 |
| Priority date | — |
| Expiry date | May 30, 2015 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY10S977/92
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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-n…
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