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; Takeo Kuwata; Shokichi Takahama; Yu Kaku; Shashwata Biswas; Kaho Matsumoto; Hirokazu Tamamura; Shuzo Matsushita

doi:10.1186/s12977-021-00568-y

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

Retrovirology. 2021 Aug 21;18(1):23. doi: 10.1186/s12977-021-00568-y.

Authors

Hasan Md Zahid¹, Takeo Kuwata¹, Shokichi Takahama^{1

2}, Yu Kaku¹, Shashwata Biswas¹, Kaho Matsumoto¹, Hirokazu Tamamura³, Shuzo Matsushita⁴

Affiliations

¹ Division of Clinical Retrovirology, Joint Research Center for Human Retrovirus infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
² Laboratory of Immunosenescence, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
³ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Division of Clinical Retrovirology, Joint Research Center for Human Retrovirus infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. shuzo@kumamoto-u.ac.jp.

Abstract

Background: 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. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections.

Results: We 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.

Conclusions: These 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.

Keywords: ADCC; C1C2 antibody; CRF02_AG; HIV-1; Non-neutralizing antibody; Non-subtype B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / isolation & purification
Antibodies, Neutralizing / immunology*
Antibodies, Neutralizing / metabolism
Antibody-Dependent Cell Cytotoxicity
CD4-Positive T-Lymphocytes / immunology
HIV Antibodies / immunology*
HIV Envelope Protein gp120 / immunology*
HIV Infections / immunology*
HIV-1 / classification
HIV-1 / immunology*
Humans
Immunoglobulin G / immunology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp120
Immunoglobulin G