Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

Urai Chaisri,Wanpen Chaicumpa

doi:10.1155/2018/9747549

Abstract

This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be produced in vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients) are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

Highlights

Antibodies are glycoproteins of the immunoglobulin superfamily
Immune B cells derived from immunized or disease convalescing subject can be immortalized by infecting with Epstein-Barr virus (EBV); the virus transformed-immune B cells are cloned; individual clones grown in vitro similar to the mouse hybridoma culture and the secreted human monoclonal antibodies can be harvested from their culture supernatants [39,40,41,42,43]
By means of contemporary technologies, antibodies that are fully biocompatible to the human immune system for a safe passive immunization against infections and noninfectious diseases can be generated in vitro without a prolonged in vivo immunization process

Summary

Introduction

Antibodies are glycoproteins of the immunoglobulin superfamily. Antibodies are produced by plasma cells which are derived from differentiated B lymphocytes of the immune system in response to foreign substances. Maternal antibodies are known to interfere with vaccine immunogenicity in infants It is difficult (and sometimes impossible) to induce active immune response against highly toxic substance that the immunogenic dose is higher than the disease causing dose. A combination of active and passive immunization has been practiced for intervention of rabies in rabid dog bitten subjects whose bite wounds are serious and/or located near to the central nervous system In this instance, human rabies immune globulins (HRIG) and rabies vaccines are given concomitantly at different sites; the former is for providing immediate immunity (the HRIG is infiltrated around the biting wound and injected intramuscularly) and the latter for eliciting a longer lasting immunity to the virus [5]. Antibodies may be an adjunct of supportive therapy for infections/intoxications that direct acting agents are not available or for infections caused by drug resistant pathogens [10]

Therapeutic Antibodies

10 GRAKKFNIT

Influenza and Influenza Viruses

Immunotherapy of Influenza and Perspective

Findings

Conclusions