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. 2005 Jan;79(2):780-90.
doi: 10.1128/JVI.79.2.780-790.2005.

Antibodies that are cross-reactive for human immunodeficiency virus type 1 clade a and clade B v3 domains are common in patient sera from Cameroon, but their neutralization activity is usually restricted by epitope masking

Chavdar Krachmarov  1 , Abraham Pinter, William J Honnen, Miroslaw K Gorny, Phillipe N Nyambi, Susan Zolla-Pazner, Samuel C Kayman
Affiliations

Antibodies that are cross-reactive for human immunodeficiency virus type 1 clade a and clade B v3 domains are common in patient sera from Cameroon, but their neutralization activity is usually restricted by epitope masking

Chavdar Krachmarov et al. J Virol. 2005 Jan.

Abstract

Sera from human immunodeficiency virus type 1 (HIV-1)-infected North American patients recognized a fusion protein expressing a V3 loop from a clade B primary isolate virus (JR-CSF) but not from a clade A primary isolate virus (92UG037.8), while most sera from Cameroonian patients recognized both fusion proteins. Competition studies of consensus V3 peptides demonstrated that the majority of the cross-reactive Cameroonian sera contained cross-reactive antibodies that reacted strongly with both V3 sequences. V3-specific antibodies purified from all six cross-reactive sera examined had potent neutralizing activity for virus pseudotyped with envelope proteins (Env) from SF162, a neutralization-sensitive clade B primary isolate. For four of these samples, neutralization of SF162 pseudotypes was blocked by both the clade A and clade B V3 fusion proteins, indicating that this activity was mediated by cross-reactive antibodies. In contrast, the V3-reactive antibodies from only one of these six sera had significant neutralizing activity against viruses pseudotyped with Envs from typically resistant clade B (JR-FL) or clade A (92UG037.8) primary isolates. However, the V3-reactive antibodies from these cross-reactive Cameroonian sera did neutralize virus pseudotyped with chimeric Envs containing the 92UG037.8 or JR-FL V3 sequence in Env backbones that did not express V1/V2 domain masking of V3 epitopes. These data indicated that Cameroonian sera frequently contain cross-clade reactive V3-directed antibodies and indicated that the typical inability of such antibodies to neutralize typical, resistant primary isolate Env pseudotypes was primarily due to indirect masking effects rather than to the absence of the target epitopes.

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Figures

FIG. 1.
FIG. 1.
Serum reactivity with V3 fusion proteins by ELISA. (A) Sera (1/150 dilution) from 23 HIV-1-infected patients from Cameroon were assayed by ELISA against the clade A (filled bars) and clade B (open bars) fusion proteins. (B) Sera (1/100 dilution) from 47 HIV-1-infected patients from North America were assayed by ELISA against the clade A (filled bars) and clade B (open bars) fusion proteins. The right-most serum was a Cameroon serum previously shown to have similar reactivity with the two V3 fusion proteins.
FIG. 2.
FIG. 2.
Serum reactivity with V3 fusion proteins by RIP. [35S]cysteine labeled culture supernatant from cells producing the indicated V3 fusion protein was immunoprecipitated with the indicated serum at a 1/100 dilution and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography.
FIG. 3.
FIG. 3.
Serum adsorption on V3 fusion proteins. Sera were fractionated by adsorption to the indicated V3 fusion protein affinity resin, followed by elution in pH 2.5 buffer. Whole sera (▪), depleted column flowthrough samples (▵), and pH 2.5 eluates (○) were assayed for ELISA reactivity against each of the V3 fusion proteins as indicated. A405 is plotted versus reciprocal serum dilution.
FIG. 4.
FIG. 4.
Neutralization of SF162 by V3-reactive antibodies. Virions derived from pNL4-3. Luc.R−E− were pseudotyped with SF162 Env and used in luciferase neutralization assays. Percent neutralization is plotted as a function of antibody concentration. (A and B) Antibodies purified from sera on clade B fusion protein (•) and antibodies purified from sera on clade A fusion protein (○). (C) MAbs IgG b12 (▵), 2G12 (▴), 2F5 (⋄) (bottom panel), 447-52D (○), 4117C (•), 2557 (□), and 2558 (▪) (top panel).
FIG. 5.
FIG. 5.
Neutralization of JR-FL and 92UG037.8 by V3-reactive antibodies from Cameroonian serum 56. Virions derived from pNL4-3/Luc were pseudotyped with JR-FL Env (A) or 92UG037.8 Env (B) and used in luciferase neutralization assays. Percent neutralization is plotted as a function of antibody concentration. V3-reactive antibodies isolated on clade B fusion protein (○) and V3-reactive antibodies isolated on clade A fusion protein (•) are shown. In panel A, the MAbs are as follows: IgG b12 (▵), 2G12 (▴), 2F5 (⋄), 447-52D (○), 4117C (•), 2557 (□), and 2558 (▪). In panel B the MAbs are as follows: IgG b12 (▵), 2G12 (▴), 2F5 (⋄), 447-52D (○), 2601 (•), 2557 (□), and 2558 (▪).
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