Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity.

Abstract

Twenty-five 13-to 35-amino-acid-long peptides representing regions of human immunodeficiency virus type 2 (HIV-2), strain SBL6669, envelope proteins were evaluated for their immunogenic activity in guinea pigs. The peptides were selected to provide homologous representation of sites in the HIV-1 envelope proteins that were previously documented to have a particular immunogenic importance.

Human immunodeficiency virus type 2 (HIV-2) env gene analysis: prediction of glycoprotein epitopes important for heterotypic neutralization and evidence for three genotype clusters within the HIV-2a subtype

“…This supports the proposal of it being a domain sensitive to neutralization by heterotypic antibodies, despite the low antigenicity of such peptides derived from HIV-2 (de Wolf et al, 1991) and HIV-1 (Neurath et al, 1990). Peptide 380-404 maps to the amino terminus of the C3 domain, but similar HIV-2-derived peptides have low antigenicity (de Wolf et al, 1991;Norrby et al, 1991) and immunogenicity and do not induce neutralizing antibody (Bjorling et al, 1991).…”

“…All have positive indices, indicating hydrophilicity and therefore probable surface expression, with peptides 170-193, 512-528 and 747-764 being the most hydrophilic. Of these three, only peptide 512-528 is highly immunogenic (de Wolf et al, 1991 ;Norrby et al, 1991) and similar peptides are able to induce strainspecific neutralizing antibodies (Bjorling et al, 1991). Peptide 329-358 maps to the HIV-2 V3 loop which by virtue of high immunogenicity, together with studies of its genetic variability (Boeri et al, 1992) identifies this domain as a potential target for neutralizing antibody, an observation supported by independent reports (Bottiger et al, 1990;Bjorling et al, 1991Bjorling et al, , 1994.…”

“…Of these three, only peptide 512-528 is highly immunogenic (de Wolf et al, 1991 ;Norrby et al, 1991) and similar peptides are able to induce strainspecific neutralizing antibodies (Bjorling et al, 1991). Peptide 329-358 maps to the HIV-2 V3 loop which by virtue of high immunogenicity, together with studies of its genetic variability (Boeri et al, 1992) identifies this domain as a potential target for neutralizing antibody, an observation supported by independent reports (Bottiger et al, 1990;Bjorling et al, 1991Bjorling et al, , 1994. However, analyses performed in the present study to determine which epitopes on HIV-2cBL2 ~ glycoprotein might be recognized by neutralizing antibodies present in HIV-1 positive human sera (Schulz et al, 1990) did not select the V3 domain, a result which agrees with other studies (Robert-Guroff et al, 1992).…”

“…Peptide 628-659 maps to the glycosylated domain of gp41 and in the context of a non-glycosylated peptide is able to induce neutralizing antibodies in guinea-pigs (Bjorling et al, 1991). The position and local environment of a glycosylation sequon (N-X-S/T) in a protein can affect the degree of occupancy and processing of any carbohydrate added (Opdenakker et al, 1993).…”

“…Three reports * Author for correspondence. Fax +44 81 906 4477. e-mail r-daniel@nimr.mrc.ac.uk (Bottiger et al, 1990;Bjorling et al, 1991Bjorling et al, , 1994 have identified the homologue of the V3 loop, the principle neutralizing domain in HIV-I (Javaherian et al, 1989), as a target for neutralizing and, in one study (Bottiger et al, 1990), cross-neutralizing antibody. However, another group (Robert-Guroff et al, 1992) found no binding of cross-neutralizing antibody to the V3 loops of several strains of HIV-2.…”