Viral-Induced Enhanced Disease Illness

Abstract

Understanding immune responses to viral infections is crucial to progress in the quest for effective infection prevention and control. The host immunity involves various mechanisms to combat viral infections. Under certain circumstances, a viral infection or vaccination may result in a subverted immune system, which may lead to an exacerbated illness. Clinical evidence of enhanced illness by preexisting antibodies from vaccination, infection or maternal passive immunity is available for several viruses and is presumptively proposed for other viruses. Multiple mechanisms have been proposed to explain this phenomenon. It has been confirmed that certain infection- and/or vaccine-induced immunity could exacerbate viral infectivity in Fc receptor- or complement bearing cells- mediated mechanisms. Considering that antibody dependent enhancement (ADE) is a major obstacle in vaccine development, there are continues efforts to understand the underlying mechanisms through identification of the epitopes and antibodies responsible for disease enhancement or protection. This review discusses the recent findings on virally induced ADE, and highlights the potential mechanisms leading to this condition.

COVID-19 vaccine design: the Janus face of immune enhancement

“…Antibody-dependent enhancement ADE is a second concern and generally results when non-neutralizing antibodies bind to newly infecting virus to promote enhanced virus uptake into host cells via Fcγ receptors (FcγRs) 8 . Perhaps the best known example of ADE occurs following infection with multiple dengue virus serotypes, first reported by Halstead and O'Rourke in the 1970s and now influencing the design of new dengue vaccines.…”

Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (ADE)

“…This multi-pronged approach provides coronaviruses like SARS-CoV-1, MERS-CoV, and SARS-CoV-2 with more than one mechanism for infecting host cells. This leads to the hypothesis that antibody mediated uptake of virus is the potential mechanism that induces ADE to vaccines and can also be mediated by maternally transferred antibodies (matAbs) [60][61][62][63] .…”

“…Many of the viruses associated with ADE have cell membrane fusion mechanisms 61 . For influenza A H1N1, vaccine-induced anti-HA2 antibodies promote virus fusion causing vaccineassociated enhanced respiratory disease (VAERD) 79 .…”

An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

“…We fabricated adjuvanted microspheres for this study as a room temperature stable dry powder using the Flow Focusing process to be 11µM in diameter so as to prevent more than one microsphere from being phagocytosed by any given antigen presenting cell (APC) at the same time [37]. By loading only one peptide 55 sequence per microsphere, we maximized the peptide payload and mitigated the possibility of multiple, different peptide sequences being delivered to the APC simultaneously, which could possibly result in competitive inhibition at the motif which could interfere with antigen presentation and subsequent T-cell expansion (Supplementary Material Section 1). 60 We also set out to see if a similar approach to a CTL vaccine design for SARS-CoV-2 would be feasible based on an analysis of the HLA binding characteristics of peptide sequences on SARS-CoV-2 nucleocapsid.…”

“…CoV-2, unlike a typical antibody vaccine, is not limited to virus surface antigen targets. This provides opportunities to attack other targets on SARS-CoV-2 besides spike which may be prone to mutation[74].In addition, a peptide vaccine mitigates the risk of Antibody Disease Enhancement (ADE) seen in the context of a non-neutralizing antibody response to 360 a whole protein vaccine[75][55]. Also, neutralizing antibodies directed against spike protein in SARS-CoV-1 patients have been associated with an increased risk of Acute Lung Injury (ALI)[35].…”