An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies.
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 pathogens. 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 an HIV vaccine.
Evans
D J
DJ
Department of Microbiology, University of Reading, UK.
McKeating
J
J
Meredith
J M
JM
Burke
K L
KL
Katrak
K
K
John
A
A
Ferguson
M
M
Minor
P D
PD
Weiss
R A
RA
Almond
J W
JW
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D002678:Chimera; D005796:Genes; D005814:Genes, Viral; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D015483:HIV Antibodies; D015488:HIV Antigens