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Journal of Virology, February 1999, p. 1740-1745, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1 Isolate with Sera from Naturally Infected Individuals

Simon Beddows,1 Simon Lister,1 Rachanee Cheingsong,1 Claudine Bruck,2 and Jonathan Weber1,*

Department of GU Medicine and Communicable Diseases, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom,1 and R&D Extramural Research, SmithKline Beecham Biologicals, 1330 Rixensart, Belgium2

Received 16 June 1998/Accepted 21 October 1998

We have characterized sera from healthy volunteers immunized with a monomeric recombinant gp120 (rgp120) derived from a CCR5/CXCR4 (R5X4)-using subtype B isolate of human immunodeficiency virus type (HIV-1), HIV-1W61D, in comparison to sera from long-term HIV-1-infected individuals, using homologous reagents. Sera from vaccinees and HIV-1 positive subjects had similar binding titers to native monomeric rgp120W61D and showed a similar titer of antibodies inhibiting the binding of soluble CD4 (sCD4) to rgp120W61D. However, extensive peptide binding studies showed that the overall pattern of recognition of vaccinee and HIV-1-positive sera is different, with vaccinee sera displaying a wider and more potent recognition of linear V1/V2 and V3 domain epitopes. Neutralization of homologous HIV-1W61D or heterologous HIV-1M2424/4 peripheral blood mononuclear cell (PBMC)-derived virus lines by vaccinee sera could be achieved, but only after adaptation of the viruses to T-cell lines and was quickly lost on readaptation to growth in PBMC. Sera from HIV-positive individuals were able to neutralize both PBMC-grown and T-cell line-adapted viruses. Interestingly, rgp120W61D was recognized by monoclonal antibodies previously shown to neutralize primary HIV-1 isolates. The use of very potent adjuvants and R5X4 rgp120 led to an antibody response equivalent in binding activity and inhibition of binding of sCD4 to gp120 to that of HIV-positive individuals but did not lead to the induction of antibodies capable of neutralizing PBMC-grown virus.

* Corresponding author. Mailing address: Department of GU Medicine and Communicable Diseases, Jefferiss Trust Laboratories, Imperial College School of Medicine at St. Mary's, Praed St., London W2 1PG, United Kingdom. Phone: 44 171 886 1539. Fax: 44 171 886 6645. E-mail: j.weber{at}ic.ac.uk.

Journal of Virology, February 1999, p. 1740-1745, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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