Antigen Expression Kinetics and Immune Responses of Mice Immunized with Noninfectious Simian-human Immunodeficiency Virus DNA

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 Nov 12

PMID 16282469

Citations 7

Authors

Ramakrishna Hegde

Zhenqian Liu

Glenn Mackay

Marilyn Smith

Yahia Chebloune

Opendra Narayan

Dinesh K Singh

Affiliations

Soon will be listed here.

Abstract

In a previous report we demonstrated that three injections of an rt-deleted noninfectious genome of the simian-human immunodeficiency virus SHIV(KU2) induced protection against AIDS in macaques (D. K. Singh, Z. Liu, D. Sheffer, G. A. Mackay, M. Smith, S. Dhillon, R. Hegde, F. Jia, I. Adany, and O. Narayan, J. Virol 79:3419-3428, 2005). To make this DNA safer, we deleted two more genes, the integrase gene and vif, along with the 3' long terminal repeat. We also replaced the gag, pro, and nef genes (SIVmac239 origin) with those of human immunodeficiency virus (HIV) type 1 strain SF2. The resultant construct, designated delta4SHIV(KU2) DNA, was used in this study to evaluate gene expression and immunogenicity in BALB/c mice. DNA-transfected human embryonic kidney epithelial cells (HEK 293) produced all of the major viral proteins and released p24 in the supernatant for 12 days. Inoculation of the vaccine DNA into the gastrocnemius muscles resulted in intense mononuclear cell infiltration at the inoculated sites and the production of viral p24 in myocytes, in infiltrating mononuclear cells, and in cells in the spleen and draining lymph nodes between 3 and 10 days postinoculation. Expression of p24 in the muscle cells peaked at day 7 and became undetectable after day 12. The same 12-day period of expression of p24 was observed in mice that were given a second injection 4 weeks after the first. Evaluation of immune responses in BALB/c mice revealed that the DNA induced enzyme-linked immunospot and antigen-specific proliferative cell-mediated immunity responses. The responses were stronger in mice that were coinjected with a second plasmid expressing granulocyte-macrophage colony-stimulating factor. Since new waves of viral antigen production could be induced with each boosting injection of the vaccine DNA, this DNA could be a safe and efficient agent to induce long-term protection against HIV.

Citing Articles

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DNA immunization site determines the level of gene expression and the magnitude, but not the type of the induced immune response.

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Induction of cell-mediated immune responses in mice by DNA vaccines that express hepatitis C virus NS3 mutants lacking serine protease and NTPase/RNA helicase activities.

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Immunogenicity of a lentiviral-based DNA vaccine driven by the 5'LTR of the naturally attenuated caprine arthritis encephalitis virus (CAEV) in mice and macaques.

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Characterization of T-cell responses in macaques immunized with a single dose of HIV DNA vaccine.

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PMID: 19923181 PMC: 2812351. DOI: 10.1128/JVI.01846-09.

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