Functional analysis of a monoclonal antibody reactive against the C1C2 of Env obtained from a patient infected with HIV-1 CRF02_AG

Hasan Md Zahid,Shuzo Matsushita,Shokichi Takahama,Takeo Kuwata,Kaho Matsumoto,Hirokazu Tamamura,Shashwata Biswas,Yu Kaku

doi:10.1186/s12977-021-00568-y

Abstract

BackgroundRecent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and the C1C2 region mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections.ResultsWe isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to the C1C2 of gp120, and 1E5 binds to 27 out of 35 strains (77 %) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and 4E9C (anti-CoRBS antibody), but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-C1C2 antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of 1E5, A32 and 4E9C mediated a strong ADCC activity.ConclusionsThese results suggest that anti-C1C2 antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.Graphical abstract

Highlights

Recent data suggest the importance of non-neutralizing antibodies in the development of vaccines against Human immunodeficiency virus type 1 (HIV-1) because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and the C1C2 region mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells
Isolation of monoclonal antibody 1E5 from a donor infected with CRF02_AG B cells from a donor infected with CRF02_AG were transformed by Epstein–Barr virus (EBV) and the supernatants were screened for reactivity to the envelope glycoprotein trimer (Env) of HIV-1 93TH966.8 (CRF01_AE) strain
The binding activity of 1E5 to Env proteins from various HIV-1 strains was examined by flow cytometry (Fig. 1a)

Summary

Introduction

Recent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and the C1C2 region mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. Most of the nnAbs mediating ADCC require Env in a CD4-bound conformation [8] and target epitopes that overlap epitopes recognized by the anti-C1C2 antibody, such as A32 [9,10,11]. These CD4-induced (CD4i) immunoglobulins (IgGs) are present in the sera, breast milk and cervicovaginal lavages of HIV-1-infected patients [12, 13]

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