Coronavac inactivated vaccine triggers durable, cross-reactive Fc-mediated phagocytosis activities.

Although humoral responses elicited by infection or vaccine lost the ability to prevent transmission against Omicron, vaccine-induced antibodies may still contribute to disease attenuation through Fc-mediated effector functions. However, Fc effector function elicited by CoronaVac, as the most widely supplied inactivated vaccine globally, has not been characterized. For the first time, our study depicted Fc-mediated phagocytosis activity induced by CoronaVac, including antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent neutrophil phagocytosis (ADNP) activities, and further compared with that from convalescent individuals and CoronaVac recipients with subsequent breakthrough infections. We showed that 2-dose of CoronaVac effectively induced both ADCP and ADNP, but was substantially lower compared to infection, whereas the booster dose further augmented ADCP and ADNP responses, and remained detectable for 52 weeks. Among CoronaVac recipients, ADCP and ADNP responses also demonstrated cross-reactivity against Omicron subvariants, and breakthrough infection could enhance the phagocytic response. Meanwhile, serum samples from vaccinees, convalescent individuals with wildtype infection, BA.2 and BA.5 breakthrough infection demonstrated differential cross-reactive ADCP and ADNP responses against Omicron subvariants, suggesting the different subvariants of spike antigen exposure might alter the cross-reactivity of Fc effector function. Further, ADCP and ADNP responses were strongly correlated with Spike-specific IgG responses and neutralizing activities, indicating coordinated neutralization activity, ADCP and ADNP responses triggered by CoronaVac. Of note, the ADCP and ADNP responses were more durable and cross-reactive than corresponding Spike-specific IgG titers and neutralizing activities. Our study has important implications for optimal boosting vaccine strategies that may induce potent and broad Fc-mediated phagocytic activities.

Combination treatments with hydroxychloroquine and azithromycin are compatible with the therapeutic induction of anticancer immune responses.

Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.