Anti-spike IgG exacerbates lung injury by skewing monocyte-macrophage responses during SARS-CoV infection

Abstract

Abstract Deceased SARS patients displayed severe acute lung injury (ALI) with exuberant inflammatory responses yet faster neutralizing IgG development. The mechanism underlying this discrepancy remains elusive. Here, we combine vaccination and passive immunization strategies to determine whether anti-spike (S) IgG modulates SARS-CoV-mediated lung injury in Chinese rhesus macaques. We found that macaques pre-vaccinated with MVA-S displayed more severe lung injury compared with MVA-vaccinated controls after SARS-CoV challenge. Moreover, passive immunization of purified anti-spike IgG but not control IgG resulted dose-dependently in enhanced lung infection and severer lung injury, associated with prolonged responses of pro-inflammatory alveolar MAC387+ and CD163+TGF-b− macrophages, IL-6 production and delayed wound-healing CD163+TGF-b+ macrophages response. Consistently, accumulated pro-inflammatory CD163+TGF-b− macrophages were found in lungs of deceased SARS patients. Our results demonstrated that anti-spike IgG exacerbates lung injury likely by enhancing infection and skewed alveolar monocyte-macrophage responses, which may have significant implications to CoV-mediated pathogenesis and immunotherapy.