From Cowpox to COVID-19: A Brief Overview of Vaccination

Copyright free photo from Christian Emmer

Inquiries seeking updates about the COVID-19 vaccine are no doubt common Google searches nowadays. The vaccine is the light at the end of the tunnel—the key that will set the world free from the nightmare of this pandemic. People might be marvelling at the fact that they have gone from dreading the word shot as a child (or maybe even older than that) to actually hoping against hope to be poked in the arm in the near future. 

What exactly makes this arm-poke so powerful? The vaccines of today operate by using some disease-causing agent or part of one, such as a dead virus or a part of a viral protein, to train the body’s immune system to be able to mount an attack against it. The body’s immune system mounts a small-scale attack against what’s in the vaccine, which is like the rehearsal before the big production. That way, when the body encounters the real live disease, the immune system already has experience against its kind and can fight it better. 

This principle of training the immune system has its roots in the technique of variolation, which was developed by practitioners in Asia, as long ago as in the 12th century. Variolation is “the deliberate infection with smallpox” [5]. The practitioners blew dried smallpox scabs into the nose of the patient, who then contracted a mild form of smallpox. The mortality rate of smallpox infection by variolation ranged from 1-2 percent, as opposed to 30 percent in naturally-contracted cases of smallpox [5]. When variolated individuals recovered, they were then immune to the disease. 

In the early 18th century, Lady Mary Wortley Montague, the wife of a British ambassador in the Ottoman empire, learned about the practice and demanded that it be tested on prisoners. Instead of having scabs blown in the nose, smallpox was injected under their skin. When the prisoners were deliberately exposed to smallpox, none got sick. The royal family then received the procedure, which went on to become fashionable in Europe [5].

Variolation was not without risk, however. Aside from the questionable ethics of the variolation techniques used on unsuspecting prisoners and the possibility of death from the procedure (a vaccine with a 1-2% mortality rate would never be deemed fit for use today), there was also the very real possibility that the mild disease contracted by the patient could spread and cause an epidemic [5]

Edward Jenner is credited with being the first person to provide scientific support of the practice of vaccination. Tales of his day said that dairymaids were protected against smallpox if they had had cowpox, a minor disease. In 1796, Jenner took matter from the cowpox lesions of a dairymaid and inoculated an eight-year-old boy with the matter. The boy developed a mild fever but then recovered within nine days of the inoculation. Two months after the cowpox inoculation, Jenner injected the boy with matter from a smallpox lesion. The boy developed no disease [6]. After performing this experiment on a few more cases, he published a booklet on his findings, in which he coined the term “vaccination,” from the Latin vaccinia, meaning cowpox [6]. Subsequently, the practice of vaccination took hold in Europe and later in the United States.

Needless to say, vaccines today do not still contain their namesake cowpox. Instead, the most common vaccines of today largely fall into four vaccine types [8]. Vaccines can contain a live, attenuated virus. This is the most similar to the original cowpox vaccine. Just as cowpox is a milder poxvirus than smallpox, an attenuated virus is weaker than its natural form. The difference is that attenuated viruses are modified in a lab to make them weaker so as to stimulate an immune response but not cause illness in otherwise healthy individuals [8]. Examples of common live attenuated vaccines are the varicella (chickenpox) and shingles vaccines. 

Vaccines can also be inactivated or killed. In a lab, the virus is inactivated, usually using formaldehyde as an agent. “Formaldehyde exerts its effect by a great diversity of modifications… which culminate in inactivation, stabilization, or immobilization of proteins with consequent loss of viral infectivity” [7]. Examples of this type of vaccine include the polio and rabies vaccinations. Another type of vaccines are subunit, recombinant, or conjugate vaccines, which use specific parts of the disease causing agent, like a protein or capsid casing. The vaccine uses these key bits to train the body to recognize that specific protein or capsid, and mount a targeted response accordingly [8]. Common examples of this type of vaccine are the vaccines against HPV and Hepatitis B. A final type of vaccine are toxoid vaccines, which function in a similar fashion to subunit vaccines. Toxoid vaccines use a harmful product made by the disease agent to “create immunity to the parts of the germ that cause disease instead of the germ itself” [8]. 

There are more than 90 vaccines in development against SARS-CoV-2, the virus that causes the COVID-19 infection [1]. Some vaccines are being developed using attenuated or inactivated forms of the SARS-Cov2 itself. Two of the frontrunners, the candidates from Johnson & Johnson and AstraZeneca, are viral-vector vaccines, a type of subunit vaccine [1]. This means that a virus such as adenovirus is “genetically engineered so that it can produce proteins in the body”. The adenovirus is a vector that delivers a gene from the SARS-Cov2 virus into the cells of the body, which “will read it and make coronavirus spike proteins” , which will cause an immune response [2]. The adenovirus itself is weakened, or attenuated, so it cannot cause disease, and key genes that allow the adenovirus to replicate have been disabled. No vaccines using this vector method have been approved yet for humans; although adenoviral vectors have a long history in gene therapy [4]

Two more frontrunners, the vaccines from Moderna and Pfizer, are using even more novel technology. They are mRNA vaccines. mRNA is a molecule with instructions to make proteins. In this case, proteins that help the virus replicate [4]. Once the mRNA from the vaccine is in the cell, the ribosomes of the cell start using that mRNA template to create SARS-CoV-2 spike proteins. These proteins coat the surface of the virus and are harmless on their own. The immune system then perceives the spike proteins as if the body has been infected by the actual virus, resulting in antibody creation [3]. If this mRNA technology proves effective on a large scale, it could change the way vaccines are manufactured. Rather than go through the long process of growing and inactivating an “entire germ or its proteins in a specific way,” as is necessary for all the previously mentioned vaccine techniques, scientists can instead manufacture pieces of mRNA that could prove more flexible and durable against viruses that evolve through mutation [9].

Much like variolation and Jenner’s vaccine led the charge against smallpox, a disease which caused the world much suffering, the scientists behind today’s vaccines against COVID-19 infection are actively fighting to do the same. Whether using cowpox, attenuated virus or viral mRNA, vaccines throughout history are designed to do the same thing: to help our bodies keep us safe in the face of a formidable disease.

Edited by: Soyi Sarkar

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