Modifications of HIV-1 retrovirus-like particles to enhance safety and immunogenicity.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Modifications of HIV-1 retrovirus-like particles to enhance safety and immunogenicity.

Biologicals. 1998 Dec;26(4):255-65. Unique Identifier : AIDSLINE MED/99331461
Persson RH; Cao SX; Cates G; Yao FL; Klein MH; Rovinski B; Pasteur Merieux Connaught Canada Research Centre.

Abstract: HIV-1 retrovirus-like particles can be produced in VERO cells that have been transfected with an expression construct encoding HIV-1 structural proteins. The particles are entirely non-infectious although structurally they resemble infectious virus particles. This makes them a promising candidate for use as an HIV-1 vaccine. In order to ensure their safety and enhance their immunogenicity, the retrovirus-like particles were modified in a number of ways. A large deletion in the HIV-1 pol gene has eliminated reverse transcriptase and integrase activities. Deletion of RNA packaging signals in the RNA untranslated leader sequence and in Gag reduced packaged RNA to 5% of that in HIV-1 virus. Replacement of the existing HIV-1LAI envelope protein with that of HIV-1MN has ensured that immune responses to the particles are relevant to those against the majority of HIV-1 clade B isolates. In addition to these changes in particle composition, yields of the modified particles were increased using a superior method of inducing the expression construct promoter, and an effective scheme for particle purification was developed. Immunization of non-human primates demonstrated that the particles were capable of generating anti-HIV-1 neutralizing antibodies. The technological refinements reported here will permit retrovirus-like particles to be tested safely in humans, and the change in envelope proteins should allow a more realistic evaluation of the immunogenicity of these particles. Experience gained in engineering these refinements will greatly facilitate other modifications that may be required to achieve maximum efficacy as a vaccine against HIV-1.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Animal AIDS Vaccines/GENETICS/*IMMUNOLOGY Cercopithecus aethiops Consumer Product Safety Gene Expression Gene Products, gag/GENETICS/IMMUNOLOGY Human HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY HIV-1/GENETICS/*IMMUNOLOGY/PHYSIOLOGY/PATHOGENICITY HIV-1 Reverse Transcriptase/GENETICS/METABOLISM Macaca mulatta Molecular Sequence Data Peptide Fragments/GENETICS/IMMUNOLOGY Support, Non-U.S. Gov't Vaccines, Synthetic/GENETICS/*IMMUNOLOGY Vero Cells Virion/PHYSIOLOGY Virus Assembly
991130
A99B1092

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