[Commentary] Study revealed Antibody-dependent enhancement (ADE) of CCP Virus infection

Author: MOS Ben Edwards

Scientists in Osaka University, Japan recently published an article entitled “An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies” in the world-leading journal Cell, reporting antibody-dependent enhancement of SARS-CoV-2 (the CCP virus) infection.

Antibody-dependent enhancement https://doi.org/10.1016/j.cell.2021.05.032

According to the report, the CCP Virus, an enveloped positive-strand RNA virus, requires fusion with the host cell membrane for infection. The spike protein (S protein) is the major envelope protein in CCP Virus and consists of S1 and S2 subunits. The S1 subunit is further divided into an N-terminal domain (NTD) and a receptor-binding domain (RBD). The interaction between the RBD and the host cell receptor, angiotensin-converting enzyme 2 (ACE2), is believed to be mainly responsible for the infection of host cells.

A series of anti-spike monoclonal antibodies against RBD suppress the infection of CCP Virus to host cells, and they are referred to as neutralizing antibodies. Nevertheless, another series of anti-spike monoclonal antibodies against NTD, referred to as enhancing antibodies, can enhance the infection of CCP Virus to host cells.

Importantly, the report revealed that a specific subset of antibodies—8D2, 2210, 2369, 2490, 2582, and 2660—targeting the NTD domain were found to enhance the binding of ACE2 to the spike protein. The author found that the binding of ACE2 to the spike protein increased in the presence of the enhancing antibodies, even upon the addition of a neutralizing antibody C144 at concentrations up to 1 μg/ml. The study also revealed that enhancing antibodies facilitate CCP Virus infectivity.

The author also found the mechanism of enhanced infectivity of CCP Virus to host cells by enhancing antibodies. They screened a series of anti-spike monoclonal antibodies from CCP Virus patients and found that some antibodies against NTD induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of CCP Virus.

The author speculated that the enhancing antibodies’ presence might correlate with disease severity. The enhancing and neutralizing antibodies were not detected in uninfected individuals, whereas both were detected in severe CCP Virus patients. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during CCP Virus infection.

Moreover, the author identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency.   Certain pathogens with proteins similar to the NTD of CCP Virus may be involved in the production of enhancing antibodies in some uninfected individuals. There is a possibility that the production of enhancing antibodies might be boosted by CCP Virus infection or vaccination.

Consequently, in this study, the author found a non-canonical, Fc receptor-independent ADE mechanism. The antibodies against a specific site on the NTD of CCP Virus spike protein were found to directly augment the binding of ACE2 to the spike protein, consequently increasing CCP Virus infectivity.

This study provides evidence of a pandemic outbreak of the CCP virus. The truth of the CCP Virus was first exposed by the Whistleblower Movement and the New Federal State of China leading by Mr. Miles Guo. Let’s expose the crimes of the Chinese Communist Party and take the CCP down together.



Proofread/Posted by Mr. Z

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