The Right Vaccine Can Be Good.
Few would disagree – us included – that vaccines per se are a good thing. Over the decades vaccines have been created that have eradicated or allowed the prevention of truly horrible diseases such as smallpox, polio, measles, hepatitis A & B, mumps, diptheria and whooping cough. Those of you over a certain age will remember that strange event at school involving a piece of metal being heated up before stamped onto your upper arm, resulting in that little bump on your skin that you carry around for life. Ask anyone who had it what it is and they will almost certainly say ‘that’s my BCG’ even if they can’t remember for what it stands for – Bacillus Calmette–Guérin – or the disease it prevented: tuberculosis. The BCG was phased out 15 years ago in the UK, only because instances of tuberculosis became so few that administering it as a general vaccine was no longer required. A lesson that it would be prudent to remember now.
Having hyped-up the ‘killer virus of death’ (the one that continues to not kill people, especially the ones it protects) and destroyed firstly the economy and now society with its completely incorrect response, the government is falling over itself in the rush to peddle the rush job, corners-cut, adverse side effects ignored, clinical trials overlooked, wonder vaccine BNT126. After all, such a deadly stimulus can only be ‘cured’ with an equally deadly response.
Factors Influencing Any SARS-CoV-2 Potential Vaccine.
Again, vaccines in themselves are a good thing. For the right underlying disease.
However, given the:
- mortality rate of SARS-CoV-2: less dangerous than seasonal or winter flu A(H1N1)/(H3N2) and as it attenuates no more dangerous than cold-causing beta coronavirus HCoV-HKU1 or HCoV-OC43;
- average age of those dying: 82.4 years;
- comorbidity correlation: at +0.96 almost all of those who died had a comorbidity that was the underlying cause of death with SARS-CoV-2 being the exacerbating factor, as would have been A(H1N1) or enterovirus or simply the colder temperature;
- narrow focus of those at high risk: those with ACE2 downregulation and dysfunction of the renin-angiotensin system and/or dysfunction of the ACE2→ angiotensin1-7→ Mas receptor axis and counterfunction ACE→ angiotensin II→ AT1 receptor axis;
a vaccine is not required. Neither will it be effective.
The pattern recognition receptors on the leukocytes and natural killer cells that form the innate immune response are programmed to recognise the pathogen-associated molecular patterns in coronaviruses’ RNA through toll-like receptors 7 & 8. Coronaviruses have been around for millenia and have been causing the common cold for the same period.
Memory CD4 and CD8 TEM and TCM cells of the adaptive immune response are recognising SARS-CoV-2 nonstructural proteins nsp7, nsp13 and the nucleocapsid structural protein, through MHC I & II expression. These memory cells have been created through previous exposure to other beta coronaviruses, as outlined above.
Your immune system has seen enough of SARS-CoV-2 before to be able to deal with it now.
Mess With Self/Non-Self At Your Peril.
Vaccines that are both effective and safe take years, even decades to develop. They involve several levels of animal then human trials. They must be shown to have been effective before they are licensed for general use. In general they also rely upon the pathogen that the vaccine is created to protect against being high stability, so completely unlike the antigen shift and antigen drift on the spike glycoprotein of SARS-CoV-2, as well as ignoring the combined role of nsp10 & nsp16 in encoding the 5′-end of the mRNA with a Cap-1 rather than Cap-0 form to aid immunoevasion. These are not measures that make SARS-CoV-2 more dangerous, simply measures it takes to ensure its own survival.
The vast majority of vaccines are live-attenuated or inactivated and in this respect they present themselves to the immune system as ‘non-self’. The most important and fundamental principle of the immune system is its ability to differentiate ‘self’ from ‘non-self’. Without this, the immune system would attack each & every single healthy cell it encountered.
Experimental vaccines come in many forms and try to go one better than live-attenuated and inactivated. They will usually attempt to use one or more vectors (delivery methods) to get past the immune system and then gain cellular access before bioactivation (itself often the last in a series of stages of bioactivation). To do this, they have to appear as close to ‘self’ as possible while being ‘non-self’. This increases the risk of a friendly-fire incident where the usually clear line between self and non-self is blurred and the innate immune system makes a mistake, most likely through detecting the non-self underneath and then believing that other self cells are really non-self when they are not.
This is autoimmunity, worse still immunopathology and even worse still – in mRNA vaccines designed to create antigen-specific antibodies – antibody-dependent enhancement (ADE), which is where a vaccine or antiviral makes the illness worse.
You Were Born With A Degree Of Immunity.
Remdesivir as an antiviral was signed-off and approved by the US FDA in a hurry – with exactly the same symptoms of short-cuts, ignored adverse side effects and lack of evidence it actually worked – in October. We analysed its efficacy and concluded it didn’t and should be avoided apart from for a very narrow, focused group of patients with very specific complex conditions. A month later, the WHO concurred with our view. Again, there is a lesson there to be learnt.
Through the existence of TLR7 as one of your pattern recognition receptors, you were born with a degree of immunity to alpha and beta genera coronaviruses. Over 50% of people have a SARS-CoV-2-specific immunity arising from memory TCM and TEM cells, primed by previous infection with a beta coronavirus through the homology of the protein sequences, respond to SARS-CoV-2.
The healthy do not need a vaccine as their immune system can cope.
The frail (not elderly per se) with compromised immune systems have little if any immunological memory so a vaccine will not work.
Live-attenuated and inactivated vaccines maintain the fundamental self/non-self nature of the immune system. These types of vaccines are safe and effective and should always be welcomed. Experimental vaccines do not. An experimental vaccine approved and peddled as a wonder drug without side effects really is too good to be true. One clinical trial of Remdesivir showed that it killed 17% of those to whom it was prescribed, with the drug causing acute kidney failure leading to death.
Time will tell just how many checks & balances and safety protocols were either not undertaken or ignored in the rush to come up with a wonder drug.
Remember Thalidomide.
