Vaccines – Why they are Amazing, and Why we Should Not Compromise their Integrity for Speed

As most of the communities are stuck in a tense stalemate with now infamous SARS-CoV-2, a.k.a. COVID-19, many of us look to the horizon for the hints of a safe and effective vaccine. It would enable us to resume our normal lives, but more importantly, prevent millions of premature deaths from infection itself, reduced healthcare access for other conditions and increase in poverty due to economic damage.

The emergence of the new human viruses, especially those jumping from animal hosts, is nothing unusual, simply a matter of time and chance, it happened many times before. What really baffles me is a widespread attitude of mistrust in science and medicine. From simple denial of the existence of virus, to challenging motives and safety of any proposed measures. There is a justified concern that many will simply refuse to take vaccine if one becomes available.

On the other hand, there is a big political pressure to cut corners and speed things up a bit in development of COVID-19 vaccine. This is understandable in some ways, but also completely unacceptable. We must assure that safety and integrity of all public health measures. Not just because this vaccine will likely be administered to billions of people, but because we must strengthen and not weaken already shaken trust in science and public health.

We saw approval of vaccine in Russia without completed trials and published data, and there are hints that FDA may be considering similar steps in the USA. Many prominent doctors and scientists are waving red flags and ringing alarm bells [1]. As tempting as it may seem I’m convinced that lowering the bar on evidence for approval would ultimately cause much more harm than good, even if the proposed vaccines turn out to be completely safe and effective in the long run.

Motivated by this background, I want to share my personal view on vaccines and what I learned through studying medicine and research over the years. I feel that the real challenge in the whole confusion and conflicting messages is the one of communication. Perhaps another view and a different perspective may help a bit. I am not an expert on vaccines, but perhaps that helps in this case.

My goal is to put together a simple overview on the vaccines. What are they, the history and what impact they have had so far?

I do understand that this is emotional topic for many, I guess it is for myself in some ways. I do accept that attitude toward personal freedom and choice is different and needs to be respected. This conversation goes beyond medicine, but I also believe that this cannot change basic scientific facts about vaccines, based on decades of use and research.

Opposition to vaccination / inoculation is nothing new, Chinese Emperor K’ang had to deal with similar resistance in 1500s [2] in the first attempts of mass inoculations, so did British authorities when Smallpox vaccine was made mandatory in 1853 [3].

Why are we back here in 2020, after decades of research and evidence with billions of vaccines distributed globally? If something serious was amiss, wouldn’t it be obvious by now? In the 19th century we didn’t even understand existence of germs, now we know every molecule within them. We know how they spread, how they cause harm and how vaccines really work. We have decades of data on outcomes and safety, yet attitude toward public health by some is still decidedly Victorian.

I hope that those that are confused with conflicting messages may be motivated to do more research and come to their own conclusions.

What are Vaccines?

When I first started learning about history of vaccines, back in Medical School, I remember being struck by the elegance and simplicity of the approach. Unlike with many other interventions in medicine, e.g. medications or surgery, where we introduce various chemical compounds over certain period (sometimes years, even decades) or physically remove damaged or diseased tissue, vaccine method is generally far more subtle and indirect. Most of the hard work is done by our bodies, we simply give our immune system pre-warning of potential risk, and it learns to recognise and eliminate the threat more effectively; once exposed to the real thing.

This is about leveraging the natural behaviour of our immune system, one of our greatest gifts. It is more of an exercise then treatment when you look at the mechanism.

In theory, this minimally invasive, usually one-off approach should be relatively safe. It must be as we often give vaccines in large numbers, usually to young and healthy and avoiding harm must be priority. Safety standards must be more rigorous than for other interventions where we typically treat already sick people.

There are two main approaches to vaccination:

•  Using live microorganisms or viruses. Generally, with strains that are weaker (attenuated) than the one virus we try to prevent, but similar enough to create cross-reactivity of immune system e.g. famous use of relatively mild cowpox virus to create immunity against deadly smallpox.
• Using inactive (dead) viruses or bacteria or just targeted parts of them. They are not able to cause actual infections, but contain enough targets (usually signature proteins, also known as antigens or immunogens) to trigger immune response. These are considered somewhat safer and are becoming more common with a deeper understanding of molecular biology and advancements in the development and manufacturing of vaccines.

In the last couple of decades, we’ve been able to understand detailed molecular and genetic structure of the germs causing the diseases and gain deeper understanding of immune system. We have opened a whole world of the new opportunities for vaccines. We can now produce target proteins in labs by embedding genetic code in the other organisms like yeast, e.g. recent HPV vaccine is produced this way. [4]

Also, there is an ongoing research into another subtle vaccination method, one step further removed from the original cause - use of a targeted piece of genetic code from microorganism / virus in question. This is still to be fully proven in practice, but with some promising early signs. In this method our bodies need to do more work, first synthesizing the proteins as a target from provided genetic material and then creating an immune response. [5]

Another important part of vaccines is so-called adjuvant. This is typically a generic substance, non-specific to targeted disease, and has a role of stimulating immune response and thus helping to create sustained resistance against the virus or bacteria in question.

Based on the increasing knowledge of immunology, there is a fast-growing area of therapy and research to leverage immune response in treatment of various other conditions, most notably cancers. This is fascinating area, but here I’ll stick to infectious diseases.

The name vaccine comes from Latin ‘vacca’ for cow, as the first created vaccine was derived from cattle virus, cowpox. Interestingly, widely used vaccines for Tuberculosis, BCG is based also on cattle derived mycobacterium. We owe a lot to humble cows.

There are a lot of partially interchangeable terms around vaccines, with various dictionary definitions. Perhaps a brief clarification is in order:

• Vaccination is a process of triggering immune response in a person by introducing a vaccine. It is a specifically designed biological substance that does not cause an actual disease we are trying to prevent.
• Immunisation includes vaccination but it is a bit wider term, as it includes passive immunisation, like introducing ready antibodies from a human or animal source e.g. botulism or rabies serum.
• Inoculation is sometime referred to as a process of administering a vaccine, but historically it refers to introduction of actual smallpox pathogen, also called variolation, and is considered riskier, as it could cause a full-blown smallpox infection.

Currently, we have well established vaccines available for some 25 infectious diseases, 15 caused by virus and 10 bacterial. Many more are in the process of development or testing, including 100+ for COVID-19.

How did we come up with this weird idea of the vaccination?

Most stories start with Edward Jenner in the late 18th century England. There were reports, or folk wisdom if you like, stating that some of the women working with cows seem to be resistant to smallpox; if they had much milder cowpox symptoms before. He asked himself what if we deliberately expose people to cowpox, can we provide protection to the population from smallpox? Keep in mind that this was at the time with absolutely no knowledge on existence of germs, immunity etc. Infectious diseases were linked to things like ‘bad air’… Smallpox had 25-30% mortality and was scourge of humanity for centuries.

Jenner famously, and by today standards unacceptably, tried this on an eight-year-old boy, James Phipps, first exposing him to cowpox, and six weeks later to actual smallpox. James survived the exposure and lived to age 65, which was pretty good in Victorian England times.

Edward Jenner vaccinating James Phipps in 1796, by Ernest Board

He is not the first one to try immunisation with cowpox but was the first one to document and publish this in 1798 after some additional trials. Hence, the glory and recognition.

Please note that this was simply a replication of naturally occurring process, the goal was for people that don’t milk cows to be protected as well.

Some reports go back further, with first well documented one in 15th century China, where they used inoculation with smallpox pustules. Rather a dangerous procedure and not a true vaccination, but still at times of epidemics it was commonly used, with some claimed benefits [6]. It is difficult to assess value from this perspective. However, it did lead to some of the first public immunisation campaigns with familiar resistance we see today.

“The method of inoculation having been brought to light during my reign, I had it used upon you, my sons and daughters, and my descendants, and you all passed through the smallpox in the happiest possible manner…. In the beginning, when I had it tested on one or two people, some old women taxed me with extravagance, and spoke very strongly against inoculation. The courage which I summoned up to insist on its practice has saved the lives and health of millions of men. This is an extremely important thing, of which I am very proud.”

From letter by Chinese Emperor K’ang to his descendants. [2]

This quote is both fascinating and disappointing to see how little has changed in 500 years in acceptance of public health measures.

There was now a promising method to prevent many of the smallpox cases ravaging communities across much of the world. Developing the vaccine was almost the easier part, how to organise the manufacturing, distribution and administration countrywide or even globally was the real challenge. This was not helped by the fierce opposition. Some countries started to make vaccinations mandatory, Italy tried first and failed, then Sweden as early as 1816, followed by England in 1853. They established a very efficient method of vaccinating children when pustules developed on their skin, this created the source of the vaccine for next round. Quite gruesome and unsanitary by today’s standards, but certainly meant low cost and no lack of vaccines. (4,6,7,8]

This was met with various anti-vaccination movements, whose motivation varied from religious, to political, sanitary or scientific. Various Leagues were formed with Leicester, England being consider as the centre of the movement. Similar trends were seen in the U.S. with an increase in numbers of dedicated organisations to stop vaccination against smallpox. [9]

Besides slowing progress down, opposition movements were not able to stop the process of smallpox vaccination, likely due to obvious benefits. However, it did take almost 200 years to eliminate all cases.

So why is this important? Look at the graph below. After the targeted vaccination for smallpox, it simply run out of space to spread. The approach was meant to create rings around known cases and vaccinate those that are most likely to be exposed, not entire populations. The last known case was reported in 1977. It is believed that some military labs in the U.S. and Russia still have samples of the virus, but there is no spread in the human population. As there are no new cases, we don’t need vaccination against smallpox anymore. If we eliminate the disease, we can stop vaccinations for that disease. The smallpox vaccine was not perfect, no vaccine is, but many of us own our existence to it. If smallpox claimed the lives of our parents or grandparents at a young age, many of us would have never been born.

Had oppositions of the smallpox vaccination been successful, imagine what could have been the consequences with the sharp rise in human population, urban density and global travel. This virus has similar mechanism of spreading like COVID-19, but it was 30-50 times more deadly. With today’s modern treatment methods and technology; the mortality of smallpox would have been significantly lower, but certainly still disastrous. Best estimate available, by Hinman and UNICEF is that we would have some five million people dying from smallpox every year. [10]

Creation and mass distribution of this vaccine was from my perspective one of the greatest achievements of the science and human society in general. Smallpox eradication was finally completed as a true international effort with WHO (World Health Organisation) at the centre of it. Perhaps there is a lesson for us to learn from this… But I digress, let me go back to history.

Other notable vaccines

Polio

Polio is short for poliovirus, and the disease it causes, poliomyelitis. It is also known as infantile paralysis, a vicious disease, attacking mostly children, many without notable symptoms, but for some causing neural infections and consequent paralysis of muscles. This can include muscles used for breathing, causing affected children to slowly choke to death. Those that survive these symptoms were often left with permanent brain damage or paralyzed.

Partial relief came when the early version of respirators became available, infamous ‘iron lungs’. Wards like the one on the image below were common in many cities in the U.S. and Europe until 1960s when the first vaccines became available. Some affected children would regain breathing capability after a week or two, some would not and would spend rest of their lives, months or even years, within the ‘iron lungs’. [11]

Image from polio hospital ward in U.S. in 1952

This dire situation led to an effort to create a vaccine, with two separate and probably equally important results. One from the U.S. led by Jonas Salk, an inactivated vaccine, administered through injection. Efficacy was proven by now famous trial, including a large control group that received a placebo. These trials were supported by a new foundation, The March of Dimes whom collected dimes from the U.S. population in local shops. This effort was further supported through the likely misdiagnosed link of Franklin D. Roosevelt’s condition to polio.

Campaign to collect donations – send dimes to the White House for fighting Infantile Paralysis

When asked who owned the patents for the vaccine, Jonas Salk famously answered “Well, the people I would say. There is no patent. Could you patent the sun?” [12] Dr Salk doesn’t strike me as an evil corporate guy with some hidden agenda behind the vaccine.

Other vaccine one came from the Soviet Union, led by Albert Sabin. His vaccine was a weakened virus taken orally. This proved to be more effective, easier and cheaper to distribute due to oral administration, but somewhat riskier because people were ingesting a live virus. In rare occasions there were examples of it mutating back to original form, out of 10 billion doses distributed there were 760 such cases reported. [13]

So, was it worth it? Today, most of the world has no new cases. There are only a few spots in Afghanistan and Pakistan where the virus remains in circulation. WHO just recently announced Africa to be polio free after 4 years of no new cases. Complete eradication of poliovirus is within the reach. The number of lives saved, disabilities averted, and health resources spared is impossible to quantify. For me the knowledge that our children don’t run a risk of ending up on a respirator or paralysed from polio is a compelling argument why vaccines can be such a wonderful tool. [14]

BCG (Bacille Calmette–Guérin)

BCG is a vaccine designed to help prevent Tuberculosis (TB). Tuberculosis is still one of the leading causes of death among infectious diseases The TB vaccine is only partially successful in preventing infection or serious complications. Tuberculosis appears in two major forms, as meningitis, especially with young children and pulmonary. Protection from this vaccine is much more reliable for the first form, but it does reduce severity of pulmonary forms as well.

This is a live vaccine, based on bacteria from the same group as the one causing TB in humans. Again, we benefit from cross-reactivity of the immunity to related germs. Beside some local reaction, the vaccine is considered safe. Sometimes it can cause stronger local infections of lymph nodes requiring treatment. Because this is a live vaccine it is not used with patients that have compromised immune system.

It has been in the use since the 1920s in Belgium and France and globally starting in the 1950s. One serious incident was registered in 1930s when a more aggressive strain was given to newborns in Germany. It was determined that the vaccine was contaminated due to inappropriate storage. We have not seen similar cases in the following decades and in the billions of doses administered.

What’s interesting about this vaccine is that it does not generate only specific immunity for tuberculosis, but that it also could improve non-specific immune response to other conditions. E.g. it is a treatment option for some forms of bladder cancer and various forms of respiratory infections, sepsis and infant mortality in general are lower for children that received BCG. There is compelling evidence around this, and multiple ongoing research to test exact effects, including the prevention of Diabetes Mellitus type 1 and against COVID-19. [15]

Tuberculosis has been brought under control in many western countries by combining the BCG vaccine, antibiotic therapy and better living conditions. TB is still a very deadly disease in large parts of the world and there is certainly a need for further investments in both prevention and therapy.

DTP (Diphtheria Tetanus Pertussis) Vaccine

This vaccine is the combination of three vaccines against bacterial diseases. There is a lot of resources available about them, so I won’t go into details. They are all potentially lethal with pertussis (whooping cough) being especially contagious, and tetanus being very deadly although not contagious between people.

This vaccine is used globally and given to more than 110 million children every year. The impact has been very significant with notable reduction in mortality from these conditions with the spread of vaccination.

It didn’t escape controversy of course.

In the 1950s a London hospital provided a provisional report about some neurological issues with children who received the DTP vaccine. This led to a decline in immunisation, which caused three major epidemics of whooping cough and associated problems. A major independent scientific review of all children hospitalised with alleged symptoms found that vaccines are safe and need to be continued. Court cases in the UK were dismissed due to lack of evidence. Similar processes were happening in the U.S. with major results leading to the increase of vaccine prices and a reduction in vaccine investment. Unfortunately, one of the consequences was the increased burden of vaccine-preventable diseases. [9]

More recently some observational studies suggesting that DTP could have opposite effect on non-specific immunity to BCG. Potentially increasing the risk of other infections. The WHO has done a comprehensive review and found no evidence to support these claims. [16] There is ongoing research into non-specific effect of this and other vaccines, some findings warrant further examination, and may potentially lead to some fine tuning of the vaccine schedule.

Overall, there is agreement that the vaccine is beneficial and the risk minimal. This is based on decades of use and billions of doses administered. [17]

MMR (Measles Mumps Rubella) Vaccine

This vaccine contains live, attenuated viruses, designed to create an immunity against three dangerous diseases. For the purpose of brevity, I’ll focus mostly on measles and I encourage you to research further on the others.

Measles start with flu-like symptoms, and then develop a characteristic rash all over body. In many cases our amazing immunity will prevail, but sometimes it leads to serious complications. This includes severe pneumonia and encephalitis (brain inflammation). These complications are often lethal or with long-term consequences.

WHO estimates that in 2018 140,000 children were killed by measles. This is a sharp rise from only a few years earlier, clearly linked to a drop in the immunisation. A significant number of measle cases and deaths have been reported in Europe, which was considered free from measles until recently. [18]

 Child with measles

The MMR vaccine attracted a lot of attention from a paper by Andrew Wakefield in 1998 that has since been retracted and discredited. [19] He suggested a possible link between bowel disease, autism and the MMR vaccine. Data in this paper was found to be falsified by British Medical Journal (BMJ), and Wakefield did not declare a conflict of interest, he was paid to investigate evidence for vaccine related litigation. [20,21]

This unfortunate episode was enough to increase resistance to the vaccinations in general and specifically for MMR. This has clearly led to the reduced coverage of the vaccine and unfortunately rise in the cases and preventable deaths from these diseases.

Many independent studies have been conducted, comparing in total millions of vaccinated and non-vaccinated children. None of them found any correlation between autism and MMR vaccine. [22] From medical evidence perspective, this is as clear as it gets. It is also very clear that this episode contributed to unnecessary deaths of thousands of children around the world.

Interestingly, there is some evidence emerging that MMR as a live (attenuated) vaccine has benefits of increasing non-specific immunity, similar like BCG. This seems to help reduce risk from other, especially respiratory infections. More research is needed here, but certainly is potentially significant. [23]

Many other vaccines – Hepatitis B, Flu, Pneumococcal, HPV, Rotavirus etc.

As this article is already getting a bit lengthy, I’ll skip details on these vaccines, but please investigate them further if you’re interested. All of them can be lifesaving.

For example, HPV vaccine has potential to prevent almost 100% of cervical cancers.

Are vaccines dangerous?

Like any health intervention, vaccines have some risks. Therefore, it is essential to have a rigorous evaluation prior introduction to widespread use and it is equally important to have robust monitoring and reporting on any possible long-term or rare side effects that can potentially be missed during initial trails. [24]

As vaccines are often administered in huge numbers and to healthy individuals and children, safety standards must be higher than for the any other health intervention. Even small or rare harm across large populations can be very significant. That’s why despite having more than 100 candidates for COVID-19 vaccines, it should take 6-12 months to have one approved, if at all. They are undergoing trials to establish if they are safe and effective. Of course, as already mentioned, some attempts to lower the bar on standards because of urgency of situations must not be allowed.

The advantage we have today with vaccines is that many have been used for decades, with billions of doses administered, so we have a much clearer picture of them versus any other medication or procedure I can think of.

From what we know, in most cases risks are very low and side effects typically mild, like redness, soreness, mild temperature, typical signs of inflammation - immune system responding to the stimulus.

For inactive vaccines usually the biggest risk is serious allergic reactions, which can be dangerous but are very rare. [25] If they happen, these reactions are usually evident within minutes of receiving the vaccine.

With live vaccines, there are chances for serious infection, or sometimes a mutation to the original more aggressive form. Again, this is very rare. This is the reasons they are normally not given to patients that have compromised immunity, either due to an illness or a medication. There is a growing research interest in the potential ability of live vaccines, like BCG or MMR, to give a boost to general, non-specific immunity. There are several trials ongoing investigating this effect in relation to COVID-19. [26,27,28]

If there were some patters of unknown significant harm, these would clearly be visible after worldwide distribution over many decades. Some of the vaccines mentioned above like DTP or MMR are given to more than 100 million children every year.

Suggesting that there are serious issues with existing vaccines, being hidden by millions of doctors, nurses and scientists around the world for me is difficult to understand. This is simply not feasible from what I understand about how the healthcare system works. It would also be illegal in almost every country, against medical ethics, and I would say basic humanity.

Since we started mass vaccination, child mortality has dropped significantly along with the big rise of the overall life expectancy. Of course, there are many other factors in play here, but still this must be reassuring. This was what vaccines were made for in the first place.

I studied medicine and have been personally interested over years in understanding ratio of benefit and risk for various medications and intervention available. Different vaccines come with different risks and benefits. If we look at them as a group, not ideal, but perhaps helpful in this context, my view is there is no intervention that offers more benefits for such low risk and at such low cost.

Just for the record I don’t think that’s always the case for many other therapies or procedures.

My biggest gripe with the vaccines is that we don’t have more of them.

Are vaccines a good business?

Despite a lot of noise suggesting otherwise, from what I know, vaccines are generally not seen as a very exciting business prospect by pharma industry. Let me explain:

• Vaccines are designed to prevent infectious diseases, and unfortunately budgets available for this kind of public health activities are very limited. Of course, during a global pandemic there is keen interest and funds available for specific disease, but this is an exception. Normally, a large majority of the health budgets are spent on treatment of diseases and that’s where most of pharma companies are making the biggest investment.
• Vaccines are so efficient it’s hard to make a lot of money on them. What do I mean by this? As mentioned above, with vaccines most of the work is done by our bodies, so 1 or 2 doses is often all that’s needed. Each dose for common vaccines, cost roughly as much as a cup of coffee, and it’s usually quite easy to administer. Investing into cancer drug that if successful can sell at $100.000 per year makes much more sense from a business perspective. This is not right or wrong, just reality.
• Many of the infectious diseases that are a good potential target for the vaccines are mostly present in the developing world, and they have limited funding available to justify very large investments in the developments and the testing of vaccines.
• Some litigations around vaccines in western countries, despite lack of any serious evidence of harm have discouraged pharma companies from making further investments in this area, especially during the 1970s and 1980s.

Of course, there is a market for vaccines and several large pharma companies working on development, but unfortunately, many have no vaccine business, or it represents a small share of their revenue. If you look at overall health spend, vaccines account for a very small proportion. For example, in Western Europe no country spent more than 0.5% of their health budget on vaccination with 0.34% being average and with a tendency of decreasing share. [27]

The benefit we see in terms of reduction of deaths, disease burden and allowing us to focus health resources to other conditions in my opinion makes this investment the best value in the whole of healthcare.

What is the future for vaccines?

I think of vaccines more like an exercise for the immunity rather than an invasive intervention. As physical exercise can improve our muscle strength and cardio-respiratory capacity, by giving a nudge to our immunity we are better prepared to deal with specific or even non-specific threats in forms of viruses or bacteria.

It does come with some risks of course, they can be serious, but this is very rare. I know I repeat myself, but this is important – everything we know tells us that health benefits of vaccines by far exceed potential risks. [30,31] Our children are far more likely to come to serious harm by riding a bicycle or eating peanuts then from a vaccine. [32,33]

As mentioned, testing and monitoring for safety is not optional. Safety standards for vaccines are and should be higher than for any other intervention. I know that most of experts in this field are driven by desire to help contain or eliminate these diseases, and happily vaccinate their children. I am grateful for their work and for vaccines available today, hopefully we have more safe and effective ones to come including the one for SARS-CoV-2.

More than 100,000 children globally are dying from measles every year. [17] That number can and should be zero, or at least close to it. Europe and North America were measles-free until recently but drop in the vaccination rates led to steady raise in cases and even deaths. This is clearly dangerous and unnecessary.

Delay in effective immunisation against SARS-CoV-2 (if available) could kill millions directly and indirectly. Trying to skip the steps in the evaluations process may further fuel already existing scepticism and lack of trust. Let’s work on facts and data to come to the best way forward, it has worked for us many times in the past.

Political pressure on scientific process of developing and evaluating vaccines cannot be acceptable. Speed is good, but we cannot compromise on standards required for approval. This is essential not just for safety but for the trust in public health measures in general. Let’s accelerate laboratory work, manufacturing, distribution etc. Clinical trials require certain time and need to be done properly and with robust evidence of safety and effectiveness before proceeding.

I have two requests for those that read this, one for general public and one for the doctors, scientists and regulators.

• If you have doubts or see some conflicting messages, please don’t just share or propagate claims or theories without verifying sources and having data that confirms it. I would consider most of these claims and conspiracies around vaccines silly and amusing if they weren’t so dangerous. Undermining trust in public health and medicine can and does kill people. Please never do that lightly and without strong evidence, not if you really care about health.
• If you have a role in science, medicine or regulatory process, please let’s not allow compromises on the scientific integrity of vaccines or any other medication for that matter. This is always dangerous, but especially in these days of limited trust and alternative reality in the dark corners of the internet.

Once vaccine is hopefully available, I think it’s important for people to have choice whether to take it or not. Please just don’t forget how much choice and freedom we’ve been given by protection from all the diseases mentioned above. Not so long ago, parents were keeping their children from playing outside in summer in fear of them catching polio, every fall or scratch meant a risk of tetanus etc.

Today, many of us are fearful of hugging our parents, meeting friends, going out, travelling, because of COVID-19. Imagine freedom and choice we could be given back by having safe and effective vaccine. 

I leave you with some statistic from the U.S. on cases and mortality of vaccine-preventable diseases before and after the vaccination was introduced. Hopefully COVID-19 can be added to this list in not too distant future.

Opinions expressed here are only my own.

References

1. Eric Topol, An Open Letter to Stephen Hahn, MD, From Eric Topol, MD, Medscape, August 2020.
2. Glynn, Ian, and Jenifer Glynn. The life and death of smallpox. London: Profile Books, 2005.
3. Stewart, Alexandra J., and Phillip M. Devlin. "The history of the smallpox vaccine." Journal of Infection 52.5 (2006): 329-334.
4. Plotkin, Stanley. “History of vaccination.” Proceedings of the National Academy of Sciences of the United States of America vol. 111,34 (2014): 12283-7. doi:10.1073/pnas.1400472111
5. Schlake, Thomas, et al. "Developing mRNA-vaccine technologies." RNA biology 9.11 (2012): 1319-1330.
6. Boylston A. The origins of vaccination: no inoculation, no vaccination. J R Soc Med. 2013;106(10):395-398. doi:10.1177/0141076813499293
7. Edsall G. Smallpox Vaccination vs Inoculation. JAMA. 1964;190(7):689–690. doi:10.1001/jama.1964.0307020012503
8. Lombard, Marion et al. “A brief history of vaccines and vaccination.” Revue scientifique et technique 26 1 (2007): 29-48.
9. The History of Vaccines. History of Anti-vaccination Movements. Acessed 20/07/2020
10. Hinman, A. R. (1998). Global progress in infectious disease control. Vaccine, 16 (11-12), 1116-1121. Online here.
11. Ochmann S. and Roser M. Polio, Our World in Data, Published on November 9, 2017.
12. Smith, Jane S. Patenting the sun: Polio and the Salk vaccine. W. Morrow, 1990.
13. Platt, Lauren R., Concepción F. Estívariz, and Roland W. Sutter. "Vaccine-associated paralytic poliomyelitis: a review of the epidemiology and estimation of the global burden." The Journal of infectious diseases 210.suppl_1 (2014): S380-S389.
14. Baicus, Anda. "History of polio vaccination." World journal of virology 1.4 (2012): 108.
15. Moorlag, S. J. C. F. M., et al. "Non-specific effects of BCG vaccine on viral infections." Clinical microbiology and infection 25.12 (2019): 1473-1478.
16. Immunization Safety Review Committee, Institute of Medicine. Immunization safety review: vaccines and autism. National Academies Press, 2004.
17. Aaby, Peter et al. “Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.” BMJ open vol. 2,3 e000707. 22 May. 2012, doi:10.1136/bmjopen-2011-000707
18. World Health Organisation. More than 140,000 die from measles as cases surge worldwide. Accessed 23/07/2020
19. The Editors of The Lancet. Comment: RETRACTION:—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet. 2010; 375(9713): 445.
20. Deer, B. How the case against the MMR vaccine was fixed. BMJ. 2011; 342: c5347
21. Godlee, F., Smith, J., Marcovitch, H. Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ. 2011; 342: c7452.
22. Taylor, Luke E., Amy L. Swerdfeger, and Guy D. Eslick. "Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies." Vaccine 32.29 (2014): 3623-3629.
23. Aaby P, Martins CL, Garly M-L, et al. . Non-Specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ 2010;341:c6495 10.1136/bmj.c6495
24. Shimabukuro, Tom T., et al. "Safety monitoring in the vaccine adverse event reporting system (VAERS)." Vaccine 33.36 (2015): 4398-4405.
25. Dreskin, Stephen C., et al. "International Consensus (ICON): allergic reactions to vaccines." World Allergy Organization Journal 9.1 (2016): 32.
26. Curtis, Nigel, et al. "Considering BCG vaccination to reduce the impact of COVID-19." The Lancet 395.10236 (2020): 1545-1546.
27. ClinicalTrials.Gov. BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE). Accessed 23/07/2020
28. ClinicalTrials.Gov .Use of a Live Attenuated Vaccine as an Immune-based Preventive Against COVID-19-associated Sepsis. Accessed 23/07/2020
29. Ethgen, Olivier et al. “How much money is spent on vaccines across Western European countries?.” Human vaccines & immunotherapeutics vol. 12,8 (2016): 2038-2045. doi:10.1080/21645515.2016.1155013
30. Tau, Noam et al. “Postmarketing Safety of Vaccines Approved by the U.S. Food and Drug Administration: A Cohort Study.” Annals of internal medicine, 10.7326/M20-2726. 2020
31. DeStefano, Frank, Heather Monk Bodenstab, and Paul A. Offit. "Principal controversies in vaccine safety in the United States." Clinical Infectious Diseases 69.4 (2019): 726-731.
32. McAdams, Rebecca J., et al. "Bicycle-related injuries among children treated in US emergency departments, 2006-2015." Accident Analysis & Prevention 118 (2018): 11-17.
33. Shreffler, Wayne G., et al. "The importance of reducing risk in peanut allergy: Current and future therapies." Annals of Allergy, Asthma & Immunology 120.2 (2018): 124-127.