Simultaneous Blockade of CD209 and CD209L by Monoclonal Antibody Does Not Provide Sufficient Protection Against Multiple Viral Infections In Vivo

ABSTRACT Many virus species, including Ebola virus, Marburg virus, SARS‐CoV‐2, dengue virus (DENV) and Zika virus (ZIKV), exploit CD209 and CD209L as alternative or attachment receptors for viral cis‐ or trans‐infection. Thus, CD209 and CD209L may be critical targets for the development of therapeutic monoclonal blocking antibody drugs to disrupt the infection process caused by multiple viruses. Here, we produced a human chimeric monoclonal blocking antibody that simultaneously blocks CD209 and CD209L, namely 7‐H7‐B1. We show that 7‐H7‐B1 effectively blocks multiple pseudotyped or live viral infections in vitro, including SARS‐CoV, SARS‐CoV‐2, Ebola virus, Marburg virus, ZIKV and DENV infections. However, the 7‐H7‐B1 mAb does not provide favourable protection against Zaire Ebola virus or ZIKV infection in h CD209 knock‐in mice in vivo. Thus, our findings indicate that although CD209 and CD209L are critical for multiple viral infections in vitro, they may play only a partial role in viral infections in vivo.