Infections
Vaccinations Against COVID-19
Considerations of Different Immunization Procedures
The “new Coronavirus” and the SARS-CoV-2* pandemic caused by it is still keeping the world in suspense. The more or less strict quarantine measures (Lockdown), that continued even through the whole of April, seemed to at least succeed in limiting the increase of new illnesses. However, the price for it was a paralyzed public life and an economy on low flame. Nevertheless, worldwide there were over 4.6 million medical cases and more than 300,000 deaths were counted – according to the Johns Hopkins University (Status: 18 May 2020).
The causal therapy for COVID-19* is not currently established. Different virustatics were used “off label” (thus outside of the actual indications), for example the HIV medications Lopinavir and Ritonavir. Successes were varying; large-scale clinical studies are missing. The same applies to the malaria drug Chloroquine in combination with the antibiotic Azithromycin. Remdesivir could develop a good effect in cell cultures, but the effect in people is unclear.
So currently only symptomatic therapy remains, in particular artificial respiration with progressive respiratory insufficiency up to the extracorporeal oxygenation with complete lung failure.
Vaccination – The Rescue?
A defeated infection from the new Corona Virus possibly leaves an at least temporary immunity (18-24 months?). Nevertheless, the findings according to WHO are inconsistent: In spite of proof of Virus-RNA (positive smear) a portion of the recuperated [patients] formed no antibodies, and thus are not protected from a re-infection. If approximately 70 percent of the population exhibits blocking antibodies, it seems the danger of an epidemic is averted (“herd immunity”). Hence, at first it is logical and obvious to force such a herd immunity with a vaccine.
The economic damage from COVID-19 has now already assumed an incalculable magnitude. Therefore, politics demands the development of an effective vaccination strategy from science and research with the highest emphasis. The company that first presents an “effective” vaccine, may look forward not only to profits into the billions, but also be sure of massive support on the part of politics. That has been shown in recent legislation for the measles vaccine. Generally, vaccines are in great demand from the population, and that quite rightly: Potentially deadly illnesses like smallpox, poliomyelitis or tetanus no longer play a role today after the successful vaccination campaigns of the 1950s and 1960s.
Every Vaccination is an Intervention in the Immune System
The induction of an appropriate immune response to the vaccine with an adequate antibody formation is the desired ideal case. Is it, however, also the normal case?
Each immune system reacts as individually as its owner: While one remains completely undisturbed by dust mites and pollen, another maybe reacts with a severe allergic shock. In principle, why should that be different after a vaccination with a foreign antigen?
The standardized vaccination dose always stands opposite the individual immune system.
Different Methods for the Induction of the Correct Immune Response
The development of vaccines is very costly. From the first laboratory tests through the phases of the clinical examinations until licensing up to fifteen years can pass. Such periods are out of the question in the momentary situation. Instead, the pharmaceutical industry already signals a success for 2021 – and actually new vaccination strategies could move this goal into realistic proximity.
Until now dead or weakened (“attenuated”) pathogens were used as vaccine antigens. The increase of vaccine pathogens, the standardization of preparation of vaccine antigens and the dose-finding, require many animal experiments, voluntary test subjects – and time.
The next step consisted of the utilization of single components of the respective pathogenic agents, thus for example the virus envelopes or bacterial isolates. The interconnected reduction of immunogenic epitope leads to an improved controllability of the immune response.
With further development of genetic engineering it became possible for certain virus envelope proteins to be sequenced. Such genes are infiltrated into the genome of suitable bacteria. These are cultivated on an industrial scale in bioreactors and the vaccine antigen produced in such a way is delivered into the supernatant. Today for example, the vaccines against Hepatitis B and HPV are produced in this way. In comparison with the older methods you can manufacture substantially larger vaccine quantities like this in a much shorter time.
The newest vaccine technology is based on an at first captivating thought: SARS-CoV-2 can – like any virus – only penetrate into a host cell through a suitable cell receptor. With people that is the ACE2 (angiotensin converting enzyme 2) receptor, then the virus with its “spike protein” opens like with a key-to-the-castle. However, if the immune system succeeds in forming antibodies against the spike protein, the virus cannot infect the host cells. Now the idea is to bring encoding messenger RNA (mRNA) for the spike protein into the destination cells. These should then synthesize that spike protein in the ribosome. If it is finally set free, the immune system should form corresponding antibodies.
This approach is currently pursued by the CureVac Biopharmaceutical Company in collaboration with the University of Tübingen and the US American Moderna Biotechnology Company in cooperation with Harvard University. CureVac expects a practice-useful mRNA vaccine against SARS-CoV-2 in early summer of 2021.
Will Practice Maintain What the Theory Promises?
What sounds elegant and logical in theory, comes up against practical problems: How can the mRNA be effectively brought into the destination cells? Here “transfection amplifiers” come into use, which can actually increase the protein yield. On the other hand, the side effect profile of such amplifiers is uncertain. Thus, for example, squalene is discussed as a co-trigger of Gulf War Syndrome. Transfection amplifiers also occasionally triggered an undesirable and reverse immune strengthening: Experimental animals were more susceptible to the illness from which they should be protected, and also exhibited more severe disease progressions.
Another possibility exists in the use of “harmless” viral vectors, for example the Modified Vaccinia virus Ankara (MVA). With this the gene for the vaccine protein is infiltrated into the virus genome. The disadvantage: Here the mRNA together with the replication apparatus is brought into the destination cell and can lead to a permanent self-replication of the mRNA with the consequence of an uncontrolled protein production. The consequences for the now continually stimulated immune system are difficult to evaluate, because they can be from allergies, auto aggressive diseases and even up to malignant lymphomas from clonal hyperstimulation.
In contrast the renunciation of the transfection amplifiers or the viral vectors has the advantage that the mRNA is quickly reduced through cellular ribonuclease. However, this is accompanied again with a reduced vaccine protein production and with it less antibody titers (which questions the vaccine protection) and leads to an increased portion of extracellular mRNA. Extracellular mRNA however has the reputation of developing procoagulatory effects and forming edemas. Thus, RNA vaccines could provoke thrombosis events, heart attacks and strokes.
Conclusions
As desirable in the current situation as a possibly timely development of an effective and well tolerated vaccine against SAR-CoV-2 may be: The necessary care must not be neglected. There must remain a space for discussion of safety concerns. It makes the antibody studies from WHO on cured COVID-19 patients appear questionable, whether in principle a vaccine can at all provide sufficient protection. Furthermore, it should not be ignored that for more than 80 percent of those affected by COVID-19 present only a harmless flu infection. In Germany the lethality amounts to 4.6 percent (Status: 24 May 2020). Germany total number of illnesses 180,140. Cases of death in connection with Corona: 8,371 of which aged and multimorbid people were quite predominantly affected. The comparatively low lethality (also as awful every individual case may be!) naturally makes particularly high demands on the safety of vaccination measures. For illnesses with higher lethality (e.g. Ebola, lethality 70%!) this may be evaluated differently.
Against the background of this information a broader social discourse must also be led about the introduction of the legal sanctions in the context of this vaccine. Article 2 of the Constitution of the Federal Republic of Germany: “Everyone has the right to life and physical integrity.” The decision for or against a vaccination should necessarily remain with the individual to whom conversely all relevant information should be available.
Keywords: Immunology, vaccine, research, Coronavirus, SARS-CoV-2, Corona
An Exclusive Translated Article for P2P Supported
From the Monthly Publications of P2P
Published Aug/Sept 2020
From an article in CO.med, Volume 26, June 2020
Machine Translation by SYSTRAN, Lernout & Hauspie, LogoMedia & Promt
Translation & redaction by: Carolyn L. Winsor, P2P Consulting
© Copyright 2020, Dr. med. Johannes Ebbers, Germany
Literature
- RNA Vaccinations, www.wikipedia.org
- mRNA-Vakzine: Impfen mit Genen. Pharmazeutische Zeitung 21/2018
Translator Footnotes:
* SARS-Cov-2 is the virus itself. COVID-19 is now designated as the disease caused by the virus.
** Official English translation of: Basic Law for the Federal Republic of Germany, Article 2
- Everyone has the right to the free development of his personality as long as he does not violate the rights of others and does not violate the constitutional order or the moral law.
- Everyone has the right to life and physical integrity. The freedom of a person is inviolable. These rights may only be interfered with on the basis of a law.
