Nature 339, 385 - 388 (01 June 1989); doi:10.1038/339385a0

An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies

David J. Evans^*, Jane McKeating^†, Janet M. Meredith^*, Karen L. Burke^*, Kersi Katrak^‡, Ann John^‡, Morag Ferguson^‡, Philip D. Minor^‡, Robin A. Weiss^† & Jeffrey W. Almond^*

^*Department of Microbiology, University of Reading, London Road, Reading RG1 5AQ, UK
^†Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK
^‡National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QR, UK

THE Sabin type 1 vaccine strain of poliovirus is probably the safest and most successful live-attenuated vaccine virus used in humans. Its widespread use since the early 1960s has contributed significantly to the virtual eradication of poliomyelitis in developed countries. We have reported previously the construction of an intertypic antigen chimaera of poliovirus, based on the Sabin 1 strain, and proposed that this virus could be modified to express on its surface antigenic determinants from other pathogens¹. We describe here the construction and characterization of a poliovirus antigen chimaera containing an epitope from the transmembrane glycoprotein (gp41) of human immunodeficiency virus type 1 (HIV-1). In antibody absorption experiments, the virus chimaera inhibited neutralization of HIV-1 by antipeptide monoclonal antibodies specific for the gp41 epitope and significantly reduced the group specific neutralizing activity of HIV-1-positive human sera. Rabbit antisera raised by subcutaneous injection of the polio/HIV chimaera in adjuvant was shown to be specific for HIV-1 gp41 in peptide-binding assays and by western blotting. Moreover, the antisera neutralized a wide range of American and African HIV-1 isolates and also inhibited virus-induced cell fusion. Monoclonal antibodies against the HIV-1 derived regions of the chimaera also neutralized HIV-1. These results establish the potential of using poliovirus for the presentation of foreign antigens and suggest that Sabin 1 poliovirus/HIV chimaeras could offer an approach to the development of ah HIV vaccine.

References

1.	Burke, K. L., Dunn, G., Ferguson, M., Minor, P. D. & Almond, J. W. Nature 332, 81−82 (1988).
2.	Martin, A. et al. EMBO J. 7, 2839−2847 (1988).
3.	Murray, M. G. et al. Proc. natn. Acad. Sci. U.S.A. 85, 3203−3207 (1988).
4.	Minor, P. D., Ferguson, M., Evans, D. M. A., Almond, J. W. & Icenogle, J. P. J. gen. Virol. 67, 1283−1291 (1986).
5.	Hogle, J. M., Chow, M. & Filman, D. J. Science 229, 1358−1365 (1985).
6.	Modrow, S. et al. J. Virol. 61, 570−578 (1987).
7.	Starcich, B. R. et al. Cell 45, 637−648 (1986).
8.	Weiss, R. A. et al. Nature 324, 572−575 (1986).
9.	Ho, D. D., Kaplan, J. C., Rackauskas, I. E. & Gurney, M. E. Science 239, 1021−1023 (1988).
10.	Kennedy, R. C. et al. Science 231, 1556−1559 (1986).
11.	Chanh, T. C. et al. EMBO J. 5, 3065−3071 (1986).
12.	Dalgleish, A. G. et al. Virology 165, 209−215 (1988).
13.	Ferguson, M. et al. J. gen. Virol. 65, 197−201 (1984).
14.	Murray, M. G. et al. Science 241, 213−215 (1988).
15.	Minor, P. D., Pipkin, P. A., Hockley, D., Schild, G. C. & Almond, J. W. Virus Res. 1, 203−212 (1984).
16.	Thomas, E. K. et al. AIDS 2, 25−30 (1988).
17.	Linsley, P. S., Ledbetter, J. A., Kinney-Thomas, E. & Shiu-Lok, H. J. Virol. 62, 3695−3702 (1988).
18.	Clapham, P. R. et al. Virology 158, 44−51 (1987).
19.	Francis, M. J. et al. Nature 300, 168−170 (1987).
20.	Zagury, D. et al Nature 332, 728−731 (1988).
21.	Chakrabarti, S., Robert-Guroff, M., Wong-Staal, F., Gallo, R. C. & Moss, B. Nature 320, 535−537 (1986).
22.	Michel, M-L. et al. Proc. natn. Acad Sci. U.S.A. 85, 7957−7961 (1988).
23.	Ogra, P. L. & Ogra, S. S. J. Immun. 110, 1307−1311 (1973).
24.	Harada, S. et al. Science 229, 563−565 (1985).
25.	Ratner, L. et al. Nature 313, 277−284 (1986).
26.	van der Werf, S., Bradley, J., Wimmer, E., Studier, F. W. & Dunn, J. J. Proc. natn. Acad. Sci. U.S.A. 80, 5080−5084 (1983).
27.	Rico-Hesse, R., Pallansch, M. A., Nottay, B. K. & Kew, O. M. Virology 160, 311−322 (1987).