Is the COVID-19 pandemic a case of vaccine research gone wrong?

Live-attenuated vaccines are a type of vaccine used for smallpox and childhood diseases like measles, mumps, rubella and chickenpox, in which a weakened or “attenuated” form of the virus that causes the disease is manufactured.

Because such vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting, even life-time immune response.

The disadvantage of live-attenuated vaccines resides in the fact that, because they contain a small amount of the weakened live virus, people with compromised immune systems or long-term health problems often referred to as “pre-conditions” may be at risk.

It has now been suggested that SARS-CoV-2, the virus responsible for the COVID-19 pandemic, may have arisen from laboratory experiments to produce a live-attenuated vaccine, a process that may have included genetic manipulation.

Over time, viruses have developed strategies to avoid the human immune response, allowing them to better infect cells and replicate.

Many SARS-CoV-2 patients develop only low levels of neutralizing antibodies and suffer prolonged illness compared to SARS-CoV-1, the coronavirus responsible for the 2002-2003 pandemic, indicating that SARS-CoV-2 evades human immune surveillance more effectively.

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It is widely-known that when viruses evolve to escape immune detection, they often suffer reduced fitness and become less infectious, yet SARS-CoV-2 remains highly infectious.

SARS-CoV-2 first binds to the human cell and then undergoes a membrane fusion process to gain entry, a process which is mediated by its spike protein.

The S1 component of the spike protein contains the receptor binding domain (RBD) that binds to the human angiotensin converting enzyme-2 receptor (ACE2), while the S2 segment of the spike contains the fusion-regulating element. At the S1-S2 junction is a furin polybasic cleavage site, which is involved in the separation of the S1 from the S2 section.

The RBD constantly switches between an “up” position that allows for receptor binding and “down” position in order to evade an immune response.

For membrane fusion and viral entry into the cell to occur, the spike protein must be split at the S1-S2 junction by an enzymatic process. The furin polybasic cleavage site facilitates that process by interacting with the enzymes of the human cell surface.

How then does SARS-CoV-2, which is highly-adapted for human infection, evade the immune response?

The dynamic state of the RBD may explain the paradox. That is, the switching between an “up” position that allows for receptor binding and “down” position in order to evade an immune response.

It appears that the SARS-CoV-2 RBD exists mainly in the “down” position to avoid triggering the immune system.

The presence of the furin polybasic cleavage site not only can “pre-activate” SARS-CoV-2 for fusion and cell entry, but S1-S2 cleavage may also facilitate the adoption of the “up” conformation that is required for SARS-CoV-2 to bind to the ACE2 receptor.

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According to such a scenario, SARS-CoV-2 is protected from an immune response until the very moment infection takes place.

How is all of that related to vaccine development?

In order to produce a live-attenuated vaccine for a coronavirus, you need a RBD that is highly specific for human infection, but one that is also exposed to the human immune system.

There are no known naturally-occurring coronaviruses with a RBD highly adapted for human infection and, at the same time, containing the furin polybasic cleavage site found in SARS-CoV-2.

It is feasible, therefore, that the COVID-19 pandemic resulted from the accidental laboratory release of a coronavirus being artificially modified for the production of a live-attenuated vaccine.

(Lawrence Sellin, Ph.D. is a retired U.S. Army Reserve colonel, who previously worked at the U.S. Army Medical Research Institute of Infectious Diseases and conducted basic and clinical research in the pharmaceutical industry. is email address is lawrence.sellin@gmail.com)

(Disclaimer: The opinions expressed above are the personal views of the author and do not reflect the views of ZMCL.)