Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development

Abstract

The pandemic spread of a novel coronavirus À SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle À the risk of antibody-mediated disease enhancement. The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. We also discuss how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis.

A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

“…A safety concern for a coronavirus vaccine is the risk of vaccine-associated immune enhancement of respiratory disease (VAERD) [28]. (Balb/c) and IgG2c/IgG1 (C57BL/6) were greater than 1 in LUNAR-COV19 vaccinated animals ( Figure 5A-B).…”

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

“…Another therapeutic strategy using antibodies is intravenous immunoglobulin (IVIg) that contains polyclonal IgG isolated from healthy donors, which can be further enhanced by using IgG antibodies collected from recovered COVID-19 patients in the same geographical region as the patient. Results have been mostly positive, although many of these therapies have not been formally evaluated through a randomized, double-blind, placebo-controlled clinical trial (278). According to recent studies, IVIg can be used effectively in early stages of SARS-CoV-2 infection (before the initiation of systemic damage), reducing the use of mechanical ventilation, preventing the progression of pulmonary lesions, and promoting early recovery (268).…”

Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

“…We did not find any evidence for Fc-mediated ADE promoted by the vaccine-induced immune sera, suggesting that antibody responses induced by the vaccine vectors bear minimal risk for ADE-mediated immunopathology, a general concern in SARS-CoV-2 vaccine development (44,45). In addition, based on findings with other viruses associated with ADE, the stimulation of Th1 immunity with a strong T cell response component appears to be the way forward to develop an effective SARS-CoV-2 vaccine candidate (46). ATT ATA AAA TTA TGT ATA TAA TAT TAA TTA TAA AAT TAT GTA TAT GAT TTA CTA ACT TTA GTT AGA TAA ATT AAT AAT ACA TAA ATT TTA GTA TAT TAA TAT TAT AAA TTA ATA ATA CAT AAA TTT TAG TAT ATT AAT ATT ATA TTT TAA ATA TTT ATT TAG TGT CTA After the incubation period, virus was prepared by conventional freeze/thaw method and the virus titers of each duplicate infection was determined in duplicate on CEF.…”