Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Coronavirus Infections/therapy , Cytokine Release Syndrome/therapy , Lymphopenia/therapy , Pneumonia, Viral/therapy , Antibody-Dependent Enhancement/drug effects , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Complement Pathway, Alternative/drug effects , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Disease Progression , Immunization, Passive/methods , Lymphopenia/diagnosis , Lymphopenia/immunology , Lymphopenia/mortality , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Receptors, IgG/genetics , Receptors, IgG/immunology , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , COVID-19 SerotherapyABSTRACT
Coronavirus disease-2019 (COVID-19) pandemic has become a global threat and death tolls are increasing worldwide. The SARS-CoV-2 though shares similarities with SARS-CoV and MERS-CoV, immunopathology of the novel virus is not understood properly. Previous reports from SARS and MERS-CoV documents that preexisting, non-neutralizing or poorly neutralizing antibodies developed as a result of vaccine or infection enhance subsequent infection, a phenomenon called as antibody-dependent enhancement (ADE). Since immunotherapy has been implicated for COVID-19 treatment and vaccine is under development, due consideration has to be provided on ADE to prevent untoward reactions. ADE mitigation strategies like the development of vaccine or immunotherapeutics targeting receptor binding motif can be designed to minimize ADE of SARS-CoV-2 since full-length protein-based approach can lead to ADE as reported in MERS-CoV. The present mini-review aims to address the phenomenon of ADE of SARS-CoV-2 through the lessons learned from SARS-CoV and MERS-CoV and ways to mitigate them so as to develop better vaccines and immunotherapeutics against SARS-CoV-2.
Subject(s)
Antibody-Dependent Enhancement/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Drug Development/trends , Immunotherapy/trends , SARS-CoV-2/immunology , Animals , Antibody-Dependent Enhancement/drug effects , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Drug Development/methods , Humans , Immunotherapy/methods , SARS-CoV-2/pathogenicity , Virulence/drug effects , Virulence/immunology , COVID-19 Drug TreatmentABSTRACT
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.
Subject(s)
Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Angiotensin-Converting Enzyme 2 , Antibody-Dependent Enhancement/drug effects , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Genetic Vectors/chemistry , Genetic Vectors/immunology , Humans , Immunogenicity, Vaccine , Patient Safety , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Receptors, Virus/genetics , Receptors, Virus/immunology , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Attenuated , Vaccines, DNA , Vaccines, Subunit , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/biosynthesis , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/biosynthesisABSTRACT
Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.