The Body Scientific

by Richard Kessin

Three vaccines have passed Phase 3 tests—that last step before submitting the data to the FDA for an Emergency Use Authorization (EUA). These are the two vaccines made by Pfizer and by Moderna, both of which consist of an mRNA molecule wrapped in lipid.  When injected into muscles the vaccines produce large amounts of Spike protein that provoke the immune system.  Both vaccines provide resistance to natural infection with SARS-Cov-2. There are two caveats: only a few hundred people have been protected so far and second, we are relying on a press release, rather than data. Data will come at FDA meetings in December. 

A third vaccine made by Oxford and AstraZeneca, in which the Spike gene is inserted into a crippled adenovirus that normally infects chimpanzees, also works. When injected into humans, this hobbled virus causes muscle cells to make lots of Spike protein and to provoke the immune system to make antibodies and T-cells that provide at least temporary immunity to SARS-CoV-2 infection. It is not necessary to freeze this vaccine, and plants in India, the UK and the United states are pouring it out in hope of a coming EUA. 

A fourth vaccine by Novavax in Maryland is made from Spike protein in insect cells. The Spike protein is purified, attached to a synthetic particle, and used as a vaccine.  It does not depend on expression of genes on humans. It also seems to induce lots of antibody.

These and a number other clever vaccines produced by the tools of molecular biology should deliver a large amount of vaccine starting in December and increasing in January, February and beyond.  

And yet, there are mysteries about Covid-19, and one that seems productive to think about is why are there such are a wide range of symptoms? There are asymptomatic spreaders, there are people with mild disease, there are severely sick people who need oxygen and ventilators, and finally there are people who have had disease and who recover, but with lingering and exhausting symptoms, the so-called long-haulers. 

Let’s follow the course of an infection and suppose that a person with no underlying conditions, just wants to have a drink with friends and goes to a bar where a carrier (not sick at all) breathes out some droplets of coronavirus, each of which contains thousands of copies of the SARS-Cov-2 virus or perhaps a smaller particle is circulating in an aerosol, which can keep the virus in the air for hours. 

Our victim inhales and a bolus of virus escapes from its lipid raft onto the mucous membrane cells in the nose, throat, or lung.  The virus binds to a protein called ACE2, which has a role in controlling blood pressure, but in our case is a convenient landing site for the Spike protein on the outside of the virus.  The virus is pulled into the cell, unwraps, and starts to copy itself.  This sounds ominous and it may turn out that way, but in other cells lining the lung or throat, the alarms of the innate immune system are clanging.  

The innate immune system responds immediately to threats. It does not recognize them specifically as the adaptive parts of the immune system do (T cells and B cells), but it is always on duty and does not require two weeks to ramp up. Its receptors (detectors) face out of our cells and sample the environment for viruses, bacteria, fungi or worms, which it can distinguish. The innate immune system’s police force includes natural killers cells, which recognize virus- infected host cells and destroy the virus factory by blasting holes in the cell’s membranes.  

When the innate immune system recognizes an RNA virus, it turns on many genes that produce cytokines, interferon and other proteins that limit viral damage to the host’s cells.  If there is too much induction, the lung’s blood vessels leak and the lung can fill with fluid, as in the case of a cytokine storm. If the innate immune system is functioning, it tends to control early SARS-CoV-2 and other infections. We might infer that the DNA of very sick Covid-19 patients might contain mutations in important proteins of the innate immune system and that seems to be the case, at least for some patients, according to recent reports.  

The dance between host and virus is complex. Viruses tend to have genes that it can activate as weapons to turn off the host’s response. All this is circumvented if the human victim has antibodies to the virus, as we hope to have soon.  However, there may be some systematic way to turn other new and lethal viral infections into a milder form of any disease, perhaps by controlling the innate immune system.  Covid-19 is not going to be our last pandemic.

Richard Kessin is Emeritus Professor of Pathology and Cell Biology at Columbia University’s Irving Medical Center. He lives in Norfolk, CT. Richard.Kessin@gmail.com. He will give a course on Covid-19 at The Taconic Learning Center in January.