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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 1;90(9):4156–4160. doi: 10.1073/pnas.90.9.4156

Gene inoculation generates immune responses against human immunodeficiency virus type 1.

B Wang 1, K E Ugen 1, V Srikantan 1, M G Agadjanyan 1, K Dang 1, Y Refaeli 1, A I Sato 1, J Boyer 1, W V Williams 1, D B Weiner 1
PMCID: PMC46465  PMID: 8483929

Abstract

Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.

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Selected References

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  1. Acsadi G., Dickson G., Love D. R., Jani A., Walsh F. S., Gurusinghe A., Wolff J. A., Davies K. E. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature. 1991 Aug 29;352(6338):815–818. doi: 10.1038/352815a0. [DOI] [PubMed] [Google Scholar]
  2. Carlson J. R., McGraw T. P., Keddie E., Yee J. L., Rosenthal A., Langlois A. J., Dickover R., Donovan R., Luciw P. A., Jennings M. B. Vaccine protection of rhesus macaques against simian immunodeficiency virus infection. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1239–1246. doi: 10.1089/aid.1990.6.1239. [DOI] [PubMed] [Google Scholar]
  3. Chen Y. H., Ebenbichler C., Vornhagen R., Schulz T. F., Steindl F., Böck G., Katinger H., Dierich M. P. HIV-1 gp41 contains two sites for interaction with several proteins on the helper T-lymphoid cell line, H9. AIDS. 1992 Jun;6(6):533–539. doi: 10.1097/00002030-199206000-00002. [DOI] [PubMed] [Google Scholar]
  4. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  5. Fisher A. G., Collalti E., Ratner L., Gallo R. C., Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18;316(6025):262–265. doi: 10.1038/316262a0. [DOI] [PubMed] [Google Scholar]
  6. Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Morton W. R., Benveniste R. E. Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science. 1992 Jan 24;255(5043):456–459. doi: 10.1126/science.1531159. [DOI] [PubMed] [Google Scholar]
  7. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  8. Montefiori D. C., Robinson W. E., Jr, Schuffman S. S., Mitchell W. M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J Clin Microbiol. 1988 Feb;26(2):231–235. doi: 10.1128/jcm.26.2.231-235.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Murphey-Corb M., Montelaro R. C., Miller M. A., West M., Martin L. N., Davison-Fairburn B., Ohkawa S., Baskin G. B., Zhang J. Y., Miller G. B. Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys. AIDS. 1991 Jun;5(6):655–662. doi: 10.1097/00002030-199106000-00003. [DOI] [PubMed] [Google Scholar]
  10. Nabel E. G., Plautz G., Nabel G. J. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science. 1990 Sep 14;249(4974):1285–1288. doi: 10.1126/science.2119055. [DOI] [PubMed] [Google Scholar]
  11. Nixon D. F., McMichael A. J. Cytotoxic T-cell recognition of HIV proteins and peptides. AIDS. 1991 Sep;5(9):1049–1059. [PubMed] [Google Scholar]
  12. Tang D. C., DeVit M., Johnston S. A. Genetic immunization is a simple method for eliciting an immune response. Nature. 1992 Mar 12;356(6365):152–154. doi: 10.1038/356152a0. [DOI] [PubMed] [Google Scholar]
  13. Thomason D. B., Booth F. W. Stable incorporation of a bacterial gene into adult rat skeletal muscle in vivo. Am J Physiol. 1990 Mar;258(3 Pt 1):C578–C581. doi: 10.1152/ajpcell.1990.258.3.C578. [DOI] [PubMed] [Google Scholar]
  14. Weiner D. B., Kokai Y., Wada T., Cohen J. A., Williams W. V., Greene M. I. Linkage of tyrosine kinase activity with transforming ability of the p185neu oncoprotein. Oncogene. 1989 Oct;4(10):1175–1183. [PubMed] [Google Scholar]
  15. Weiner D. B., Liu J., Hanna N., Bluestone J. A., Coligan J. E., Williams W. V., Greene M. I. CD3-associated heterodimeric polypeptides on suppressor hybridomas define biologically active inhibitory cells. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6077–6081. doi: 10.1073/pnas.85.16.6077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Williams W. V., Moss D. A., Kieber-Emmons T., Cohen J. A., Myers J. N., Weiner D. B., Greene M. I. Development of biologically active peptides based on antibody structure. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5537–5541. doi: 10.1073/pnas.86.14.5537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wolff J. A., Malone R. W., Williams P., Chong W., Acsadi G., Jani A., Felgner P. L. Direct gene transfer into mouse muscle in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
  18. Zolla-Pazner S., Gorny M. K. Passive immunization for the prevention and treatment of HIV infection. AIDS. 1992 Nov;6(11):1235–1247. doi: 10.1097/00002030-199211000-00001. [DOI] [PubMed] [Google Scholar]

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