Development of genetic vaccines for pathogenic genes : construction of attenuated vif DNA immunization cassettes

To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. vif genes were cloned from HIV-1-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic varia...

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Bibliographic Details
Published in:	AIDS (London) Vol. 11; no. 12; pp. 1433 - 1444
Main Authors:	AYYAVOO, V, NAGASHUNMUGAM, T, FRIEDMAN, H, WEINER, D. B, BOYER, J, MAHALINGAM, S, FERNANDES, L. S, LE, P, LIN, J, NGUYEN, C, CHATTARGOON, M, GOEDERT, J. J
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 01-10-1997
Subjects:	AIDS Vaccines - genetics Amino Acid Sequence Animals Biological and medical sciences Cloning, Molecular DNA, Viral - immunology Gene Expression Gene Products, vif - genetics Gene Products, vif - immunology HIV Antibodies - analysis HIV Infections - prevention & control HIV-1 Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Medical sciences Mice Molecular Sequence Data Mutagenesis, Insertional Plasmids - metabolism Sequence Analysis, DNA Tumor Cells, Cultured Vaccines, Attenuated - genetics Vaccines, DNA - genetics vif Gene Products, Human Immunodeficiency Virus HIV-1 virus Variations Prevention Gene Lentivirinae Clone Immunopathology Rodentia Retroviridae AIDS Vaccine Sequence Experimental study Immune deficiency Infection Virus Immunoprophylaxis Vertebrata Mammalia Mouse Viral disease Animal DNA Human immunodeficiency virus Attenuated strain
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Summary:	To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. vif genes were cloned from HIV-1-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic variants were selected and the ability of these clones to induce humoral and cellular immune responses was studied in animals. The selected protective genetic variants were biologically characterized through transcomplementation assays using primary cells infected with a vif-defective HIV-1 proviral clone. Analysis of vif variants from different patients revealed that vif is highly conserved with the open reading frame remaining intact in vivo. It was shown that attenuated vif clones from HIV-1-infected subjects can effectively induce both humoral and cellular responses against Vif protein in mice. Evaluation of the cellular responses in vitro using human cellular targets infected with a clinical HIV-1 isolate showed that vif clones could induce cellular responses capable of destroying the virus. The vif variants developed in this study exhibited non-productive phenotypes, yet were capable of inducing specific immune responses against HIV-1. These constructs could be used as part of a DNA vaccine strategy for HIV-1. This vaccine adaptation strategy could be used for the development of immunogens for any pathogen resulting in cross-reactive immunity and attenuated gene pathogenesis.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0269-9370 1473-5571
DOI:	10.1097/00002030-199712000-00007