Thursday, October 22, 2020

What is Vaccine Enhancement?


Note: This post discussing the risks of vaccine enhancement is not aimed at challenging the utility of vaccines. Vaccine enhancement is a known risk that must be tested for before a vaccine goes to market. Safe vaccines have been tested against vaccine enhancement. I strongly support safe vaccines and hope that we can develop safe covid vaccines.

The question I raise here after more than two dozen people have died in South Korea after getting the flu vaccine is what happens if Covid-19 is hanging out in your liver or central nervous system and you get either a flu vaccine or a covid vaccine. What are the risks for vaccine enhancement?

Julie Steenhuysen (March 11, 2020) As pressure for coronavirus vaccine mounts, scientists debate risks of accelerated testing. Reuters.

“I understand the importance of accelerating timelines for vaccines in general, but from everything I know, this is not the vaccine to be doing it with,” Dr Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, told Reuters.

Hotez worked on development of a vaccine for SARS (Severe Acute Respiratory Syndrome), the coronavirus behind a major 2003 outbreak, and found that some vaccinated animals developed more severe disease compared with unvaccinated animals when they were exposed to the virus.

“There is a risk of immune enhancement,” said Hotez. “The way you reduce that risk is first you show it does not occur in laboratory animals.”

Studies have suggested that coronavirus vaccines carry the risk of what is known as vaccine enhancement, where instead of protecting against infection, the vaccine can actually make the disease worse when a vaccinated person is infected with the virus. The mechanism that causes that risk is not fully understood and is one of the stumbling blocks that has prevented the successful development of a coronavirus vaccine.

Covid-19 can become a chronic or perhaps dormant virus. That much has been determined. What happens if you have covid somewhere in your system and you get vaccinated? How can we prevent anti-body enhancement of coronavirus?

Wan, Y., Shang, J., Sun, S., Jai, W., Chen, J., Geng, Q, He, L., Chen, Y., Wu, J., Shi, Z., Zhou, Y., Du, L., Li, F. (2020). Molecular mechanism for anti-body dependent enhancement of coronavirus. Journal of Virology, 94 (5) e02015-19; DOI: 10.1128/JVI.02015-19.

Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.

IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.