Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and in vivo. However, the potential for the SARS-CoV-2 vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed the in vitro ADE potential of monoclonal antibodies (mAbs) derived from individuals vaccinated with the inactivated SARS-CoV-2 vaccine and compared them to those from one convalescent donor. Results: Our analysis revealed no significant difference in binding affinity or neutralizing capacity between the vaccinated and convalescent mAbs. However, the inactivated SARS-CoV-2 vaccination induced fewer ADE-inducing mAbs, particularly those targeting the Class III epitope on the receptor-binding domain (RBD) compared to those from the convalescent individual. Moreover, no significant in vitro ADE was detected in either vaccinated or convalescent sera, indicating low levels of ADE-inducing antibodies in the sera. Conclusions: An inactivated SARS-CoV-2 vaccination induces fewer ADE-inducing antibodies compared to natural infection, further emphasizing the safety of inactivated SARS-CoV-2 vaccines.

Background: During the COVID-19 pandemic, three different types of inactivated SARS-CoV-2 vaccines, namely BBIBP-CorV, WIBP-CorV and CoronaVac, were manufactured and used for vaccination in China. However, as far as we know, no comparison of their induced serum neutralization has been carried out so far, possibly due to the regional difference in vaccine distribution, the difficulty in undertaking a comprehensive evaluation, and the intention to avoid unnecessary bias in populations for a certain type of inactivated vaccine.Methods: Since all three of these inactivated vaccines are no longer produced and used for vaccination, here, we retrospectively compared the serum neutralizing activities induced by these three different types of inactivated SARS-CoV-2 vaccines. Results: Compared with unvaccinated uninfected control donors, primary inactivated vaccination (232 donors) induced increased serum neutralizing titers against wildtype SARS-CoV-2 in around 70% of donors during the first 100 days. However, the neutralization effect waned quickly after 100 days, and significantly diminished against Delta and Omicron (B.1.1.529) variants. Moreover, the newly emerged Omicron variants, such as BA.2.75, BA.4/5, BF.7, BQ.1.1, and XBB, almost fully evaded the induced serum neutralization activity. Conclusions: These three distinct types of inactivated vaccines, namely BBIBP-CorV, WIBP-CorV, and CoronaVac, induced serum neutralization in most vaccinated populations but in a short-term and variant-evaded manner with no significant difference among these inactivated vaccines.

How intracellular proteins, normally hidden from the immune system, become targets of tumor-associated antibody responses remains unresolved, as does the function of such autoantibodies encoded by tumor-infiltrating B cells (TIL-Bs). Using monoclonal antibodies (mAbs) cloned from TIL-Bs in a spontaneous hepatocellular carcinoma (HCC) model, we define a class of antigens: secreted intracellular antigens (SICAs). Tumors co-opt upregulated autophagy to release cytosolic proteins, exemplified by ALDH1L1, through HSP90-mediated autophagy-dependent unconventional secretion. The resulting autoantibodies form immune complexes at the tumor site, where the SICA is locally available, recruiting and reprogramming neutrophils into tumor-associated neutrophils that drive tumor progression. Both neutrophil depletion and loss of Fcγ receptor binding abolish this effect. Autophagy-mediated SICA secretion and the corresponding autoantibody response are conserved in HCC patients and extend to lung, breast and cervical cancers. Tumors thus reshape their secretome to hijack humoral immunity, highlighting the SICA–autoantibody–FcγR axis as a potential therapeutic target.