It is excellent news about the COVID-19 vaccination programme and the vaccination trials where both humoral and cellular immune responses to challenge, after vaccination are observed. These positive responses will be required to neutralise the virus before immune escape mechanisms can be triggered from viral mutation and evolution.
Another similar single stranded positive (+ve SS) virus (HCV) has a continuous emergence of resistant strains of virus in HCV, resulting from the quasispecies that evolve, resulting in escape mutations, due to a rapid change in viral proteins. In the case of HCV, the high level of genetic diversity of the virus hampers the vaccination progress, whereas in the case of SARSCoV-2, genetic variation has also been reported where the coronavirus accumulates about two changes per month but most do not affect the behaviour of the virus, however, one SNP causes a change on the spike from aspartic acid to glycine at position 641 of the coronavirus spike and this is thought to make the virus more transmittable or more severe. G641 variant is now more prevalent than the aspartic acid version, globally. This is a genetically distinct variant but closely related to other variants within the same genotype-designated quasi species. These successful members of the quasispecies arise as a result of weak conservation of sequence and high evolutionary selection. Highly changeable quasispecies, generated as a consequence of evolutionary pressure from human immune responses, such as from antibodies, should be taken into consideration when considering candidates for the vaccine trials.
Although we do not have any evidence that immune pressure causes RNA rearrangement or mutation of the COVID-19 genome, as often occurs in other virus species or between other species, however, it is clear that these events did take place zoonotically, resulting in the SARSCoV-2 emergence after jumping between different animal species. The existence of COVID-19 and ability to infect humans is evidence of this rearrangement through the process of zoonosis with bats, pangolin and civet cats. Frequent and rapid rearrangements in other chronic viral infections, such as, HCV often render therapeutics ineffective.
I am concerned that there may be selection pressure on the virus during the vaccination process resulting in escape variants that are even more resilient and transmittable than the current SARSCoV-2. Administering the vaccine to many immunologically naïve individuals could drive many more escape variants, forced to evolve due to immune pressure but I presume that virus genetic mutation will be monitored throughout the trials. (This process slightly reminds me of the RAG gene recombinant rearrangement activation of genes in antibody and T ell receptor differentiation but an unregulated mirror image of the process in the case of the virus, both achieving a ‘’best fit’ of the antigen). Thus, the immune response of entirely healthy individuals, that receives the vaccine, could drive viral mutation inducing unknown viral escape mechanisms that may impair recognition by human immune systems. The similar SS +ve RNA virus of HCV has rapid and frequent viral mutations.
Should scientists also be cautious about viral RNA rearrangement between different viruses and tread carefully as to which individuals are vaccinated, in case they have a chronic RNA virus that could rearrange with COVID-19? We do know that +ve SS RNA viruses mutate, like HIV and HCV and some of these viruses evolve through rearrangement of the RNA.
Could it be possible that the presence of HIV or HCV virus, as indeed many other virus strains, may enable a more dangerous evolution of escape quasi-species to arise? It was reported that the exclusion of HIV patients as vaccine recipients for COVID-19 has been described as discriminatory but perhaps it should be considered as cautionary, based on basic knowledge and understanding about the behaviour of viruses and its engagement with human immune systems. Anything that may possibly influence a high mutation rate, further enabling viral persistence by evading the innate, humoral and cellular immune responses, should be avoided. Scientists have already witnessed lymphopenia in severely affected patients due to the virus attaching to ACE2 on Th1 cytotoxic cells thus affecting the cellular response in severely affected patients. HIV attaches to CD4+ T cells via the CCR5 receptor also causing lymphopenia.
Should these factors be considered or endorsed in the selection of vaccine recipient candidates in this highly uncertain phase of experimentation, with the above considerations included in the exclusion criteria for the participants?
Do any others have any of these concerns, please discuss.
Annwyne Houldsworth Thank you, agree with your points, this much high rate of mutation could possibly lead to antigenic sin, vaccination of protective immune system.
Good and interesting question, memory of immune system can also become a curse in soklme cases, Hoskins effect (Original antigenic sin). Immune system response to an original antigenic exposure in greater extent then to subsequent virus with a related structure. Also the corona virus has RNA genome, which lacks exonuclease activity i.e proofreading of their genome and hence it has power to mutate at very fast rate.
As your query concerned about vaccination, that pre-viral exposure immunity can also lead the immune system in state of confusion if the invading vurus is a bit mutated from the one which body has been immunized, the immune system inability to mount response that is uoto the mark for eliminating the virus will be worth seeing.
Regards
Mudassir
Indeed, RNA viruses do have an extraordinary ability, in such a short time, to adapt to different environments and to infect new hosts, especially when one considers that they are ‘not life as we know it, Jim’ (reference to Star Trek).
An additional factor about COVID-19 to its ability to evade the human immune system through non-synonymous mutations producing escape mutants but it may also cause the introduction of antigenic epitopes could result in the non-neutralising antibodies being generated that could enhance viral entry into the cells. These antibodies-dependant enhancement (ADE) species bind to viruses through their FAB domains. Monocytes or macrophages have Fc receptors that bind to the Fc domain of the antibody and facilitate the virus to enter the cell. During any antibody response there is often epitope-spreading, producing a wider variety of antibody, some of which could be low quality, and non-neutralising in nature. This phenomenon has been observed in Dengue fever and other viruses as well as SARSCoV.
High affinity antibodies that block ACE2 binding have been shown to enhance ADE. When the antibody-epitope binding stoichiometry is less that that required for neutralisation, ADE is induced.
Animal studies have shown that inactivated virus, MVA encoded S-protein and DNA vaccines all caused ADE or some degree of eosinophil- mediated immunopathology.
Some of the antibodies produced could also result in autoimmune immunopathology.
Annwyne Houldsworth Thank you, agree with your points, this much high rate of mutation could possibly lead to antigenic sin, vaccination of protective immune system.
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