Introduction to Antibody Dependent Enhancement

What is/are Antibody Dependent Enhancement?

Antibody Dependent Enhancement - Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. ^[1] The clinical response on exposure to a 6 second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, 7 a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection 8 do not neutralize but rather enhance the new infection, used to explain the etiology of severe 9 disease. ^[2] Autoantibodies and antibody-dependent enhancement (ADE) are the key factors proposed in pathogenesis, leading to immune dysregulation, and cytokine storm. ^[3] In this scenario, humoral immune responses targeting cross-reactive, poorly-neutralizing epitopes can lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). ^[4] Antibody-dependent enhancement (ADE) is considered a possible mechanism underlying the development of FIP. ^[5] Scrutiny of immunogenicity and adverse effects, particularly antibody-dependent enhancement, would better help in counselling these patients undergoing vaccination. ^[6] Moreover, we showed, in B-cell and monocyte cultures and ex vivo tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). ^[7] For vaccine development, it is especially important which antibodies confer protection against SARS-CoV-2, if there is a phenomenon called antibody-dependent enhancement (ADE) of infection, and if there is cross-protection by antibodies directed against seasonal coronaviruses. ^[8] In fact, the problem of antibody-dependent enhancement was raised in the context of COVID-19 vaccines. ^[9] Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. ^[10] Eight out of 339 screened studies reported on the association between ZIKV, prior DENV infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. ^[11] The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. ^[12] In fact, the problem of antibody-dependent enhancement was raised in the context of COVID-19 vaccines. ^[13] In in vitro assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. ^[14] It has been proposed that the antibodies obtained from previous exposure to local circulating human coronaviruses or possibly SARS-CoV-2 might contribute to the development of more severe and lethal presentations of COVID-19 possibly by triggering antibody-dependent enhancement. ^[15] Antibody-dependent enhancement (ADE) of infection is an alternative mechanism of infection for viruses to infect immune cells that is mediated by antibodies and IgG receptors (FcγRs). ^[16] Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. ^[17] Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. ^[18] Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. ^[19] Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. ^[20] Furthermore, cross-reactivity of the immune reaction in these infections is an emerging issue, Covid-19 through counteracting agent subordinate upgrade as pre-existing DENV-antibodies may possibly influence Covid-19 through antibody-dependent enhancement. ^[21] These glycan motifs can lead to either immune evasion or viral neutralization by the production of cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection. ^[22] It is capable of entering immune cells through DPP4 (dipeptidyl-peptidase 4) receptors and antibody-dependent enhancement, delaying initial interferon response which supports robust viral replication. ^[23] P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. ^[24] More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. ^[25] Understanding SARS-CoV-2-induced changes such as “Th-2 immunopathological variations, mononuclear cell & eosinophil infiltration of the lung and antibody-dependent enhancement (ADE)” in COVID-19 patients provides key insights to develop potential therapeutic interventions for immediate clinical management. ^[26] Antibody-dependent enhancement (ADE) has been reported for SARS-CoV and MERS-CoV, suggesting the risk of ADE for antibody-based SARS-CoV-2 vaccines and therapeutics. ^[27] ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV and DENV may exacerbate disease. ^[28] In addition, SARS-CoV-2 can trigger hepatic injury via direct binding to the ACE2 receptor in cholangiocytes, antibody-dependent enhancement of infection, systemic inflammatory response syndrome, inflammatory cytokine storms, ischemia/reperfusion injury, and adverse events of treatment drugs. ^[29] Antibody-dependent enhancement (ADE), a phenomenon in which preexisting non-neutralizing antibodies or sub-neutralizing antibodies facilitate virus entry and replication, may be a significant obstacle in the development of effective vaccines for many viruses, including PRRSV. ^[30] Factors affecting the kinetics/titers of the elicited neutralizing antibodies (NAbs), the mean persistence time of NAbs after infection, risk of reinfection, and enhanced respiratory disease via antibody-dependent enhancement (ADE) are the main issues needing to be clarified. ^[31] In addition, the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention. ^[32] In addition, the side effects such as antibody-dependent enhancement of viral infection need to be considered, and the high cost of antibody treatment will limit the clinical application. ^[33] There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). ^[34] One of the main concerns in the development of vaccines is the antibody-dependent enhancement phenomenon, better known as ADE. ^[35] However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. ^[36] A vaccine should produce immune responses with specific and neutralizing antibodies, and without harmful effects such as the antibody-dependent enhancement that may be associated with severe acute respiratory syndrome. ^[37] Non-structural protein NS1 is conserved among flaviviruses and confers immune protection without the risk of antibody-dependent enhancement (ADE). ^[38] Among them, egg yolk immunoglobulin Y (IgY), which has high safety, high yield, and without inducing antibody-dependent enhancement, is an important biological candidate. ^[39] Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. ^[40] One possibility to explain these data is the lack of robust T-cell responses and antibody-dependent enhancement of virus replication in vaccinated people. ^[41] The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. ^[42] However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. ^[43] While preventive vaccination and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization, with the theoretical risk of antibody-dependent enhancement (ADE) of viral infection remaining undetermined. ^[44] Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). ^[45] However, the recently described accumulating mutations in the SARS-CoV-2 spike protein are challenging the efficacy of approved and investigational mAbs, whose widespread use is also hampered by their significant costs and possible side effects, including Antibody-Dependent Enhancement (ADE). ^[46] One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. ^[47] Antibody-dependent enhancement (ADE) refers to the process in which some virus-specific antibodies (generally non-neutralizing antibodies) bind to the virus and bind to some cells expressing FcR on the surface through their Fc segment, thereby mediating the endocytosis and replication of the virus and enhancing the infection of the virus. ^[48] Zika virus circulates in flavivirus-endemic regions, an ideal Zika vaccine should avoid the potential of antibody-dependent enhancement from exposure to dengue virus. ^[49] In this review, the possible role of the immunopathologic phenomena including antibody-dependent enhancement, cytokine storm, and original antigenic sin in severity and mortality of COVID-19 will be discussed. ^[50]

neutralizing antibodies without

As an ideal antigen, the domain III of the envelope protein (EDIII) of ZIKV can evoke potent neutralizing antibodies without any antibody-dependent enhancement (ADE) effect. ^[1] The immunogenicity of the SARS-CoV-2 RBD, which is located in the S1 subunit and is crucial in mediating viral entry into host cells by binding to the ACE2 receptor, has been determined to induce neutralizing antibodies without evident antibody-dependent enhancement effects and can protect animals against SARS-CoV-2 infection. ^[2] This approach is more accommodative in inducing highly neutralizing antibodies, without the risk of antibody-dependent enhancement, as well as memory CD8+T-cell immunity. ^[3]