Inactivated coronaviruses, including severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), as potential
vaccines have been reported to result in enhanced
respiratory diseases (ERDs) in murine and nonhuman primate (NHP)
pneumonia models after virus challenge, which poses great safety concerns of antibody-dependent enhancement (ADE) for the rapid wide application of inactivated
SARS-CoV-2 vaccines in humans, especially when the
neutralizing antibody levels induced by vaccination or initial
infection quickly wane to nonneutralizing or subneutralizing levels over the time. With passive transfer of diluted postvaccination polyclonal
antibodies to mimic the waning antibody responses after vaccination, we found that in the absence of cellular immunity, passive infusion of subneutralizing or nonneutralizing anti-SARS-CoV-2
antibodies could still provide some level of protection against
infection upon challenge, and no low-level antibody-enhanced
infection was observed. The anti-SARS-CoV-2
IgG-infused group and control group showed similar, mild to moderate pulmonary immunopathology during the acute phase of
virus infection, and no evidence of
vaccine-related pulmonary immunopathology enhancement was found. Typical immunopathology included elevated MCP-1,
IL-8 and
IL-33 in bronchoalveolar lavage fluid; alveolar epithelial
hyperplasia; and exfoliated cells and mucus in bronchioles. Our results corresponded with the recent observations that no pulmonary immunology was detected in preclinical studies of inactivated
SARS-CoV-2 vaccines in either murine or NHP
pneumonia models or in large clinical trials and further supported the safety of inactivated
SARS-CoV-2 vaccines.