Volume 240, December 2022, 108233Abstract

Antibody therapy is effective for treating infectious diseases. Due to the coronavirus disease 2019 (COVID-19) pandemic and the rise of drug-resistant bacteria, rapid development of neutralizing monoclonal antibodies (mAbs) to treat infectious diseases is urgently needed. Using a therapeutic human mAb with the lowest immunogenicity is recommended, because chimera and humanized mAbs are occasionally immunogenic. In order to directly obtain naïve human mAbs, there are three methods: phage display, B cell receptor (BCR) cDNA sequencing of a single cell, and antibody-encoding gene and amino acid sequencing of immortalized cells using memory B cells, which are isolated from human peripheral blood mononuclear cells of healthy, vaccinated, infected, or recovered individuals. After screening against the antigen and performing neutralization assays, a human neutralizing mAb is constructed from the antibody-encoding DNA sequences of these memory B cells. This review describes examples of obtaining human neutralizing mAbs against various infectious diseases using these methods. However, a few of these mAbs have been approved for therapy. Therefore, antigen characterization and evaluation of neutralization activity in vitro and in vivo are indispensable for the development of therapeutic mAbs. These results will accelerate the development of antibody drug as therapeutic agents.

Keywords

Antibody therapy

Antibody therapeutic agent

Human neutralizing monoclonal antibodies

Memory B cells

Infectious diseases

Viral infection

Bacterial infection

Abbreviationscoronavirus disease 2019

COVID-19

antibody-dependent enhancement

ADE

constant regions of a antibody

CH and CL

complementarity determining region

CDR

severe acute respiratory syndrome coronavirus 2

SARS-CoV-2

peripheral blood mononuclear cells

PBMCs

single-chain fragmented variable region

scFv

fragmented antigen binding region

Fab

heavy chain variable region

VH

light chain variable region

VL

reverse transcription-polymerase chain reaction

RT-PCR

enzyme-linked immunosorbent assay

ELISA

human immunodeficiency virus

HIV

receptor-binding domain

RBD

angiotensin-converting enzyme 2

ACE2

Bundibugyo ebolavirus

BDBV

Tai Forest ebolavirus

TAFV

Direct acting antivirals

DAA

C-terminal receptor binding domain of the heavy chain

Hc

N-terminal translocation domain of the heavy chain

Hn

View Abstract

© 2022 Published by Elsevier Inc.