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Thread: The Mutating Coronavirus. Are there limitations on its ability to escape immunity from post-infections or by vaccines?

  1. #1 The Mutating Coronavirus. Are there limitations on its ability to escape immunity from post-infections or by vaccines? 
    Forum Junior Double Helix's Avatar
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    The continuing scourge of COVID-19, caused by the coronavirus SARS-CoV-2, requires that the virus binds to the angiotensin converting enzyme found on the surface of lung epithelial cells, and more commonly referred to as ACE-2. It is this protein by which the viral genome enters a cell and begins to replicate. (The ACE-2 protein is therefore defined as the viral "receptor", used later in defining the viral structure.)

    This region of binding in the virus spike protein is known as the receptor binding domain (RBD), and it is this region that the mutation from South Africa has altered, which is of the most concern. Mutations in the RBD (or ones that cause changes in its structure) could prevent antibodies from neutralizing such variants, but perhaps not in their moderation of the severity of the infection.

    Unlike the coronavirus however, which can mutate significantly during and after each infection cycle, the human ACE-2 protein is highly conserved. It does not mutate to any significant extent. This requires that the mutations in the virus RBD must not dramatically change its structure, or it will lose its infectivity, or at least to a great extent.

    Recall that the number of virions to which one is exposed plays a large role in disease development. Changes in the RBD might alter this requirement if the binding affinity has been reduced by too many mutations impacting this region. Based on this observation, it would seem like the virus has a major challenge, to change enough to be resistant to immune responses from prior infections or vaccines, and retain its ability to invade cells, replicate and infect others.

    It is difficult, though not impossible, for the virus to alter its RBD and still retain its deadly nature. Perhaps time will tell about its capability to evade immunity developed by prior exposure to its most vulnerable structural element - the RBD.


    Last edited by Double Helix; January 30th, 2021 at 05:58 PM.
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  3. #2 Update on mutant strains of SARS-CoV-2 and antibody resistance. Can or will this virus escape the best vaccines? 
    Forum Junior Double Helix's Avatar
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    Francis Collins, the director of N.I.H, has released some interesting data on the extent of mutations of the coronavirus and how they impact antibody binding (1). The most significant data was largely provided by an immune-suppressed individual who had a long term, low level infection of the virus. This allowed many mutations to form, and which are being analyzed against various antibodies.

    These mutations are those resulting from changes in various specific amino acids in the spike protein's receptor binding domain (RBD), as noted in the first post. There is a direct relationship to the synthetic forms of these mutations and reduced antibody binding for this patient. Superb empirical data, to be sure. It has also been reported that convalescent plasma from recovered Covid-19 patients does not improve the condition of mild to moderately ill people, so the relevance to these findings vs. the impact of the vaccine in the real world remains to be seen. More importantly, the report does not indicate testing the affinity of these virus mutants for the ACE-2 receptor by which it infects cells, a vastly more important aspect. If these mutants had lower binding affinity for antibodies, they could very likely also have lower binding affinity for the ACE-2 protein receptor (again see earlier post). The latter would greatly reduce viral infectivity at the cellular level - the most critical.

    Finally, none of this data relates to the development and efficacy of CD-8 killer T cells (2), which are programmed after infection or vaccine to kill any cell infected with the virus, and immediately stop its production. Most vaccines would stimulate a significant number of these. These cells also have long-term memory populations which can come back and hammer repeat infections. It is also possible, based on the IgG antibody data, that other means of viral suppression may be playing a role. Other forms of antibodies, such as IgA, may also be involved in viral suppression (3).

    Slowing the mutation rate is probably more important than anything right now. But only if people adhere to the right actions. Get vaccinated, and wear masks, and do all the right things to avoid enhancing the spread of this virus. Sadly, this appears very unlikely, and unless the virus mutates to become less dangerous, which is certainly possible, it will be around for quite some time. And the level of the mutation(s) threat(s) will not be known until it shows up in rising or falling hospital admissions (and their severity) over the coming months and years.



    "Mapping Which Coronavirus Variants Will Resist Antibody Treatments"

    1. https://directorsblog.nih.gov/2021/02/09/mapping-which-coronavirus-variants-will-resist-antibody-treatments/


    "Cytotoxic T Cells"

    2. https://en.wikipedia.org/wiki/Cytotoxic_T_cell


    3. https://en.wikipedia.org/wiki/Immunoglobulin_A


    Last edited by Double Helix; June 7th, 2021 at 08:39 PM.
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    Data obtained from recent studies indicate that two vaccines remain highly effective in preventing serious infections from the recent SARS-CoV-2 variant which formed in India, and is spreading rapidly (1).

    The two vaccines where this data is available are the Pfizer-BioNTech vaccine (88% effective against symptoms) and the AstraZeneca vaccine (60% effective). It should be noted that the appearance of symptoms in some vaccinated patients does not indicate progression to a serious disease state. In most such cases, the vaccines are still preventing infections requiring significant medical intervention.

    This provides additional evidence that the virus will find it difficult to mutate around antibodies and killer cells directed against the virus receptor binding domain, as noted in earlier posts. It seems likely that all vaccines based on the mRNA for the viral spike protein will have similar efficacy. Field data from Moderna and others are pending.

    However, data from an article in Nature (2) suggests the Moderna vaccine will likely be at least as effective as the two noted above, despite a significant decrease in antibody binding affinity. Other factors are involved in immunity (as noted above in previous posts), which is why a lab study cannot provide the true level of efficacy required to understand these variants and their impact on vaccines.


    "Two COVID shots effective against India variant - English health body"

    !. https://www.reuters.com/business/hea...dy-2021-05-22/


    "COVID vaccines can block variant hitting Asia, lab study finds"

    2. https://www.nature.com/articles/d41586-021-01329-9
    Last edited by Double Helix; June 11th, 2021 at 05:21 PM.
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    The most recent blog (June 22, 2021*) from the Director of N.I.H, Francis Collins, defines important aspects of immunity to SARS-CoV-2 obtained by vaccination vs natural infection.

    There appears to be ample evidence that immunity from a vaccination using mRNA technology is superior to warding off infections from all known variants. This is likely due to the directed nature of these vaccines. The mRNA versions present only the most critical aspect of the virus structure, the receptor binding domain, instead of the whole virus.

    So immunity from an infection appears to be less likely to protect one from certain variants, and this decrease in protection is likely to increase as more variants appear. Unfortunately, they are appearing at an ever increasing rate since most of the world is not vaccinated. We could be in for some even rougher sledding on this one. If you are relying on a prior infection for your immunity, it would be wise to get vaccinated to minimize the risk from a nasty variant.


    "How Immunity Generated from COVID-19 Vaccines Differs from an Infection"

    * https://directorsblog.nih.gov/2021/0...-an-infection/
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  6. #5  
    Genius Duck Dywyddyr's Avatar
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    4 consecutive posts with no responses... this thread is becoming a blog.
    "[Dywyddyr] makes a grumpy bastard like me seem like a happy go lucky scamp" - PhDemon
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  7. #6  
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    Mutations happen quite at random. Some will give the virus an advantage and allow it to get better at transmission and virulence in a darwinian fashion. It is definitely possible that some mutations make virus escape acquired immunity through vaccines or post-infection. That is why researchers are watching it closely.
    Mutation is actually the reason this coronavirus is more dangerous than other coronaroviruses.
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  8. #7  
    Forum Junior Double Helix's Avatar
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    Quote Originally Posted by pl709 View Post
    Mutation is actually the reason this coronavirus is more dangerous than other coronaroviruses.

    Various coronaviruses are replicating and surviving in many animals, including man, without causing serious problems. They all mutate, and that is the reason they are still around. Small pox was eradicated because it did not mutate. Same as polio. Vaccines were able to eliminate them.

    Humans have a handful of other coronavirus species circulating in the global population. They cause minor respiratory symptoms, and little else. And they mutate all the time. The same is true of flu and cold viruses.

    It is not clear why this virus is more pathogenic than many other coronaviruses. Mutation of this particular virus made it more dangerous in humans, but why that is remains to be established. It is likely one or more specific mutations played a role.
    Last edited by Double Helix; July 6th, 2021 at 11:17 AM.
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