Introduction to Vaccines
In 2020, after the outburst of the COVID-19 pandemic, the word “vaccine” is constantly being thrown around in the news, social media and has managed to work its way from research labs to everyday conversation. In fact, multimillion dollar pharmaceutical companies are striving to be the first at the finish line of who can produce the most efficient vaccine in the least amount of time. It seems we are all anxious and expectant of this clear solution that will serve as an antidote not only to SARS-CoV-2, but also to the loneliness of isolation and devastating economic ruin that most countries find themselves in.
Effectively, we are all subject to what goes on in the different phases of vaccine trials. Meanwhile, we must continue to adjust to the social distancing guidelines, wear face coverings and try to minimise our exposure to prevent the virus from spreading.
In today’s article, I will provide a brief summary of the history of vaccines. Then, I will go over the main types of vaccines and how they provide immunity. Lastly, I will mention a few of the vaccines that are currently under development and some potential problems we may encounter.
History of the vaccine
The name that first appears when anyone searches for the history of vaccines is Edward Jenner. This English scientist was able to produce one of the first vaccines against smallpox in 1796, but more on him later.
Ancient Chinese Practices for Vaccines
Shockingly, there are documents from the 16th century that trace the origin of vaccines back to Ancient China. It is difficult to pinpoint the exact year, but different sources mention dates of around 200-1000 AD. This means that the Chinese were already inventing mechanisms for inoculation, albeit unsanitary, before what we consider to be the start of modern vaccination. Their technique consisted on grinding scabs from smallpox and then inhaling them through the nostrils. Thankfully, science has had much time to advance and we are no longer dependent on these unhygienic practices!
Later on, inoculation was endorsed by the Chinese royalty (Emperor K’ang) who experienced the benefits of having immunity against smallpox.
https://amhistory.si.edu/polio/virusvaccine/history.htm
Lady Montagu and the Introduction of Variolation to England
Another “step” in the history of vaccination occurred when Lady Montagu, an English aristocrat, had her son variolated from the smallpox at the beginning of the 18th century. Variolation is slightly different to vaccination. The former is the introduction of the virus into the individual, usually by intravenous means, while the latter is the use of a debilitated virus, such as cowpox in the case of smallpox immunity that still produces an immune response.
Lady Montagu is credited for introducing variolation into England after her son had successfully undergone the procedure in Turkey, where they lived. However, there is much criticism around this action because many of those who were variolated died from the disease, since they still suffered from the infection. Vaccination has a much higher rate of effective immunisation without dying from the disease.
Edward Jenner and Smallpox Vaccine
In 1796, Jenner had created the first vaccine (according to the definition that we know today). After observing how milkmaids who contracted cowpox were immune to smallpox, he vaccinated a young boy by the name of James Phipps using a sore from a milkmaid who was ill with cowpox. After a few days and mild discomfort, he then proceeded to inoculate the child with smallpox, in similar ways to how a variolation would have been carried out. Phipps remained healthy and Jenner’s hypothesis was demonstrated! The vaccine worked.
Thus, the reason why we call them vaccines is because the original vector of the vaccine material was a cow (from the Latin: vacca).
Smallpox vaccination became mandatory in the United Kingdom in 1853, approximately 50 years after its discovery. In Germany, the schedule for vaccination and revaccination took until 1874, even later.
Louis Pasteur and Rabies Vaccine
Another household name in Biology is Louis Pasteur. He challenged the idea of spontaneous generation, which led him to develop much of the technology that is used today to pasteurise milk. Pasteur also appears in our history of vaccination.
He studied rabies and created a vaccine with which he inoculated 350 people, observing only one fatality. This was a very high success rate considering it was in the year 1886 and he did not benefit from the technological advances that we have today.
Types of vaccines
Live Attenuated Vaccines
As the name suggests, these vaccines are created with a live, but debilitated form of the pathogen. Because of this, they are very effective in producing antibodies, which are necessary to create immunity. Another advantage of this particular platform is the long-lasting effect of the immune response.
However, some logical disadvantages are quickly identified. For one, the pathogen is still alive, which can be worse for those who have a debilitated immune system and cannot fight off the microbe or virus at all. Secondly, these solutions must be preserved in a refrigerator, which limits their potential to be transported.
Inactivated Vaccines
Logically, these vaccines have a killed form of the pathogen, but still manages to trigger the necessary immune response.
A drawback is that the immunity is not as long-lasting as the previous vaccine. Therefore, booster shots may be required, which are not convenient in countries with poor health records or vaccine tracking.
Subunit, Recombinant, Polysaccharide and Conjugate vaccines
These vaccines are more interesting, because they only use a specific part of the pathogen to provide immunity.
As has been discussed in my previous article an enzyme can only perform its function if the substrate binds to it correctly. The same thing happens when our T cells bind to the pathogen. In reality, these cells are not binding to the entire virus or bacteria. Instead they select what is known as antigen and then recruit other immune system cells (macrophages, cytotoxic cells, B cells) to combat the infection. This process is shown simplified below:
https://www.the-scientist.com/news-opinion/the-search-for-immune-responses-that-stop-covid-19-67769
Therefore, if these vaccines only contain the necessary antigen (in the case of SARS-CoV-2, the spike protein) then it is equally as effective in providing immunity. An added benefit is that there is really no living agent involved, so individuals with weakened immune systems can tolerate them quite well. Nonetheless, these kinds of vaccines may need boosters.
Toxoid Vaccines
These are made up of a toxic substance produced by the organism that causes the disease. Through this process, the individual does not gain immunity to the whole organism, but instead to the malicious chemical it releases.
Since SARS-CoV-2 does not produce a toxic substance (or at least, not that is known) there are no toxoid vaccines being developed to fight it.
Current vaccines that are being developed
Next, I will explain the three main vaccines that are currently being researched and tested throughout the world. Since they are the most advanced ones, they all have subgroups in Phase 3 of testing.
University of Oxford/AstraZeneca
This vaccine uses a non-replicating viral vector. This means that the genetic material coding for the spike protein has been introduced into a chimpanzee adenovirus, which is a very common vector for most vaccines. It would fall into the category of an inactivated vaccine, as it does not contain the whole genome of the virus, which can cause the illness, just the spikes.
The vaccine that has received the most media coverage these past weeks has been the joint effort of the University of Oxford and AstraZeneca. This is probably because it was one of the first to reach the last stage of testing (Phase 3) and just when everyone thought the deal was sealed, they suspended the trials.
One of the volunteers who had received a dose was unwell and the whole world held its breath, awaiting a favourable outcome. Fortunately, the condition was not linked to the vaccine and the trials were resumed. The Health Secretary of the British Parliament Matt Hancock said: “This pause shows we will always put safety first. We will back our scientists to deliver an effective vaccine as soon as safely possible.”
Let’s hope that this really is the case and that safety is the main concern in manufacturing and testing a vaccine.
Sinovac Biotech
This vaccine uses an inactivated form of the virus. As was explained above, what is injected is a debilitated SARS-CoV-2. When this is recognised by the body’s immune system, it reacts just like if it were the real pathogen, with the difference that it is not deadly, since it does not carry its usual strength.
The company claims that its vaccine is yielding results and provides immunity “after injection of two doses,” against the coronavirus in “almost 97 to 98 percent of volunteers.”
Moderna/NIAID
This vaccine uses RNA, more precisely an LNP-encapsulated mRNA (LNP= lipid nanoparticle). While RNA has not been explicitly mentioned above, it could be considered as an inactivated vaccine, as the mRNA only codes for the spike protein. The difference with the University of Oxford/AstraZeneca vaccine is that the latter uses DNA. This macromolecule is more stable than mRNA, but it does require two intermediate steps (transcription and translation) before expressing the spike protein while the mRNA only needs one (translation).
Although there may not have been as much media coverage as for the University of Oxford/AstraZeneca vaccine, there has also been a fair share of polemics over this antidote. Most of them are due to the pressures put on by the government of the United States of America on having the vaccine ready before the November presidential elections. Let’s hope no rash decisions are made before the vaccine is safe to use.
Possible problems with these vaccines
While it is certainly true that we are in desperate need of a vaccine, we cannot rush the process. Safety must be a priority because it is no use having an immune response against SARS-CoV-2 if the side effects are worse than the illness itself.
The clinical trials must proceed with normality, recording any and everything that is important and seeing the long-term effects of vaccination.
https://www.hepb.org/blog/phase-3-clinical-trials-opening-hepatitis-delta-patients/
This is an unprecedented time, as has become the slogan for 2020, so researchers and companies around the world are trying to accomplish something that would normally take 10-15 years into just 1 year. It is an incredible feat that there are already over 180 vaccine designs in different labs.
Once again, we must stay patient. It may take slightly longer than a year or five years. Until the final vaccine is distributed across the whole planet, we might even be looking at 10+ years.
What this means is that we will be living with this virus for a very long time. We have to know how to coexist with it (without being too friendly) and learn from previous mistakes (i.e. previous mass epidemics or examples of countries that have done well). Together, we will make it out of this pandemic, with a vaccine to help in the near future.
Bibliography
- Draft landscape of COVID-19 candidate vaccines. Who.int. (2020). Retrieved 29 September 2020, from https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.
- Timeline | History of Vaccines. Historyofvaccines.org. (2020). Retrieved 29 September 2020, from https://www.historyofvaccines.org/timeline#EVT_100879.
- Vaccine Types | Vaccines. Vaccines.gov. (2020). Retrieved 29 September 2020, from https://www.vaccines.gov/basics/types.
Lilly Pubillones
Trinity College Hartford
Biochemistry
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