SARS-CoV-2 immunity: review and applications to phase 3 vaccin | 🦠 Infecciones virales por Coronavirus, Ebola, Influenza, Zika, VIH.✨

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates : Part VII

Enhancement of disease
Antibody response is an important component of protective immunity during SARS-CoV-2 infection.75,76 In antibody-dependent enhancement, heterotypic (nonneutralising) antibodies might have the potential to facilitate viral entry into cells through interactions with Fc receptors or complement. Even in the absence of active viral replication in immune cells, this process might lead to the activation of macrophages, monocytes, and B cells, and IL-6, TNFα, and IL-10 production.77 Cases of antibodydependent enhancement induced by vaccines have been reported after the use of formalin-inactivated vaccines against respiratory syncytial virus and measles, and after the use of a vaccine against dengue virus.78–80 Concerns have therefore been raised regarding the potential for antibody-dependent enhancement in individuals who are infected with SARS-CoV-2 after vaccination with a COVID-19 candidate vaccine.38 The potential risk of antibody-dependent enhancement mediated by Fc receptors could be increased with mutations in the SARS-CoV-2 spike glycoprotein, which could weaken the primary host antibody response. Monocyte, macrophage, and B-cell infection might occur in numerous tissues as a result of subsequently unstable virus-antibody complexes, leading to extensive apoptosis of immune cells and the production of inflammatory cytokines.52 There was evidence of vaccine-enhanced disease after SARS-CoV-1 vaccine administration in subsequently challenged animal models.81 Yang and colleagues82 hypothesised that the molecular mechanism of enhancement might involve the interaction of antibodies with conformational epitopes in the ACE2-binding domain. A study of antibody-dependent infection of human macrophages by SARS-CoV-1 has shown the role of anti-spike glycoprotein IgG in the infection of immune cells and that antibody dependent enhancement is triggered by downstream signalling pathways of FcγRII receptors.83–85 Although previous SARS-CoV-2 exposure could have a role in antibody-dependent enhancement, candidate SARS-CoV-2 vaccines administered to small animals and non-human Review primates produced antibody-mediated protection with no signs of acute lung injury and immunopathology, as was seen after SARS-CoV-1 vaccination in animal models.75,86 Antibody-dependent enhancement poses a theoretical obstacle to vaccine development and is being carefully evaluated.52,87 The extent to which pre-existing antibodies to SARS-CoV-2 (and potentially to SARS-CoV-1) might contribute to antibody-dependent enhancement and disease severity remains in question;81 however, no evidence of antibody-dependent enhancement has been found in animal models or in humans in phase 3 clinical trials.