Wednesday, October 21, 2020

Coronavirus Vaccine Trials: How Fast is Too Fast?

      The race to a vaccine has seen unprecedented speed globally; however, if we look back at why vaccine development usually takes a while, pushing out the vaccine for political reasons may be ill-advised. And might only make this disaster worse... SARS-COV2 already does not seem to elicit long lasting immunity in humans, which makes the development of this vaccine and the stringent monitoring for long term effects all the more critical. Several trials including the mRNA vaccine from Moderna, the non-replicating adenovirus type 5 vector vaccine from CanSino, Inovio's DNA vaccine, and AstraZeneca are all deep into their trials.

    We need to be smart and look comprehensively at our history of vaccine failures along with successes to see why racing to put out a vaccine may not solve the problem in the way we hope. For example, in several different trials an increase in viral activity in a term called 'vaccine-associated disease enhancement' has been shown. Many of these trials caused disease exacerbation through immune systems, through antibodies or Th2 cells or often both. For example, Dengue Fdc cells can bind to FcR-bearing cells and actually cause antibody-dependent enhancement upon second exposure to Dengue which can result in a cytokine storm and higher viral loads, thus causing even more disease. The tragic failure of the RSV vaccine is also pertinent, as this vaccine caused an enhanced respiratory disease during subsequent infections. All trials were immediately suspended after hospitalizations and deaths occurred. It's also prudent to look at SARS COV, which bears similarity in structure and tropism as SARS-COV2, particularly in the key ACE receptor to enter cells. SARS vaccines showed that they could induce excess eosinophils and TH2 cell skewed immune responses, similar to the overactive immune responses shown in RSV vaccine trials. ADE was also observed in some SARS trials.  

    Governments should be extremely cautious and allow scientists to track the safety of vaccines before they push them out to their countries, and to millions of people globally. The SARS-COV2 vaccine should elicit a balanced T cell response, be rigorously evaluated in animals and humans, and be tracked over time before passed out to humans. Certainly there is a race against the clock to end this pandemic, but cheating time and the wisdom that comes from time may not be the intelligent move in the long run. Time may actually be on our side with this one. 


-Sammy 


https://www.nature.com/articles/s41579-020-00462-y 



    





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