In the introduction on vaccination there were a couple of questions raised to delve deeper into. In this post we’ll have a look at the following question:
Do vaccines get tested for safety in the same (rigorous) way as other drugs?
So we need to look at how drugs are tested in general and then see for evidence if vaccines undergo the same protocol. If they are not, we’ll have to address the question if they need to and if their different protocol is adequate.
When creating drugs, 2 things are important. 1) Are they effective? 2) If any, what are the side effects? The latter is equally important. You don’t want to cure a person of a disease and at the same time cause the person to die from something else due to the drug.
With vaccines this is even more important because we need to evaluate preventively administering a drug. How many people are we able to protect versus how many people are we harming and to what extend are we harming them?
Drug development goes through several phases with a pre-clinical phase where lots of tests are done in petri dishes and in animals. This approach is intended for addressing the efficacy and safety of the drug and takes many year. Up to +/- 15 years on average and a good 1 billion dollar according to the reference on wikipedia.
Other sources show us similar figures.
It’s an extensive process where many more concerns are addressed to minimize negative side-effects and ensure it does what it is supposed to do at a tolerant dose for the general population.
Without going into detail, here are some resources that describe the processes and even address problems with those processes.
“Drug discovery and development: Role of basic biological research”, Richard C. Mohsa, and Nigel H. Greig, 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725284/
“Drug safety assessment in clinical trials: methodological challenges and opportunities”, Sonal Singh and Yoon K Loke, 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502602/
When we look at vaccine development, it seems to go through the same process as chemical drugs. That is reassuring in itself.
“Clinical vaccine development”, Seunghoon Han, 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313108/
But there are differences between vaccine development and chemical drug development. I found the following list worth mentioning as it addresses the safety level and complexity.
The following differences from drug development mandates special precautions while conducting vaccine clinical trials in a pediatric population:[2,3]
- Unlike drugs, which are given to patients, vaccines are received by healthy individuals, thus the safety margin should be very high.
- As vaccines have to be stored under refrigeration, there are always logistical challenges during clinical trials considering that Phase II and Phase III are field studies.
- As healthy children also receive immunization under the national program, the trial design gets complicated due to the possibility of interference during coimmunization.
- The clinical development for vaccines for infants involves a step-down approach where safety is first tested in adults, followed by adolescents, children, and lastly infants.
- Adjuvants are incorporated into vaccine formulations to modulate and improve the immune response. The compatibility of the adjuvant with the vaccine antigen and the quality and stability evaluation of antigen/adjuvant formulation are important aspects of clinical development.
- The immune response primarily measured during early stages of vaccine development (Phase I/II) should evaluate: Amount, class, subclass, and function of each specific antibody.
- Relationship between functional and nonfunctional antibody assays.
- Kinetics of immune response such as lag time for onset, antibody persistence, seroconversion rate, and induction of immune memory.
- Components of the immune response according to mode of delivery [whether immunoglobulin A (IgA) or immunoglobulin G (IgG)].
- Quality of the antibody response: Specificity and/or epitope recognition and avidity.
- Potential for formation of cross-reactive antibodies or immune complexes.
- Immunological factors that might affect the humoral immune response as preexisting antibodies (including maternal antibodies).
- Cell-mediated immune (CMI) response and the possibility of immune interference and/or cross-reacting immune responses when vaccines containing more than one antigen or two or more vaccines are coadministered, especially to children and young infants with immature immune systems.
“The clinical development process for a novel preventive vaccine: An overview”, K Singh and S Mehta, 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
The human immunology is, apart from the brain, the least understood. The heterogeneity in response is contributing to this. This makes vaccination outcomes on an individual level very unpredictable.
“Human immune system variation”, Petter Brodin and Mark M. Davis, 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328245/
With the above information it is clear that each vaccine needs to be individually assessed for safety. How did they go through this process of development?
We see that for the corona/COVID-19 virus they are able to fast-track and get it to market in 18 months. 18 months??? Because they have experience working with prototype viruses and other corona viruses like the flu.
How does that work out with the well known flu virus? It seems to be a hit or miss (1 ; 2 ; 3). Even when vaccinated, you can still get infected although they promise milder symptoms.
So how much of a hit or miss can we expect on a more different corona virus like COVID-19 where they still need to perform much more rigorous testing yet get it onto the market in 18 months? And what if the virus mutates like the flu?
The following report went through a whole list of potentially associated side effects but almost all of them were concluded with insufficient evidence to accept or reject a causal relation. Only 1 was sufficient to conclude rejection and a few were sufficient to accept causality.
If you are interested in other vaccines you can jump to all the other ones covered.
“Adverse Effects of Vaccines: Evidence and Causality.” https://www.ncbi.nlm.nih.gov/books/NBK190013/
With a hit or miss and potential side effects on a virus where we have a lot of experience with, we have an insecure future with something like COVID-19. Because it is part of the corona family, it is open to recombination under mixed infection for up to 25%! Recombination means when 2 viruses get together, it can form a 3rd type. Kind of the child of the 2 original ones.
recombination frequencies within the coronavirus family have been calculated to be as high as 25% during mixed infection.
“SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237677/#sec0010title
I’ll conclude with the following thoughts.
In an ideal world we are able to identify the people who are at risk.
- People at risk of having side effects that are more severe than the benefit they would get from vaccination.
- People at risk of having life threatening complications from the virus when not vaccinated.
The former group should not be vaccinated. The latter group should get vaccinated. Everybody else should contract the virus and build up immunity.
This has to be evaluated per vaccine. Without the ability to evaluate this, it will remain a hit or miss.
We do not need to be good at detecting safety for the general population, we need to become good at detecting people at risk. For most people the vaccine will be safe and unnecessary. We need to know those for who it is unsafe and necessary.
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