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Vaccines are a current and recurring topic of conversation. However, this is not something new. The origin of vaccines dates back to 1802 when Edward Jenner revolutionized the fight against smallpox. He observed that people who worked with cattle often did not contract the disease during smallpox outbreaks since when dealing with cattle infected with cowpox, they developed mild pustules in the body which in turn immunized them against human smallpox (much more virulent).

Technological advances have made it possible to refine the methods to design vaccines, and today there are 3 main methods. 

Technological advances have made it possible to refine the methods to design vaccines, and today there are 3 main methods.

Before going into explaining how each vaccine works, it is important to know the basic central dogma of molecular biology.

Central Dogma of Molecular Biology

Central Dogma of Molecular Biology
In humans, DNA constitutes our genetic material, but there are certain viruses such as SARS-Cov-2 whose genetic code is stored in the form of RNA. Both DNA or RNA constitute the genetic material and are transcribed originating a molecule known as messenger RNA (mRNA). This molecule is transient and is used to originate little by little all the necessary resources so that the human being or the virus can live. Each mRNA has instructions to originate a specific element (protein) that alone is useless, but is essential to form the functional set that allows us to live. Therefore, we could say that both DNA, mRNA and protein contain the same information expressed differently.
Vaccine methodology
Source: WHO

There are three main methods of making a vaccine:

Attenuated vaccines

In this type of vaccine, the whole agent is used. It would be the method used to develop the smallpox vaccine, but more sophisticated. For this method there are different approaches generating different types of vaccines:

  1. Inactivated vaccines: consists of inactivating or destroying the pathogenic virus by chemical substances, heat or radiation. An example of a vaccine developed with this methodology is that of influenza.

  2. Attenuated vaccines: the pathogen remains weakened but active causing a much smaller infection. Sometimes this type of vaccine is not recommended for immunocompromised people and among this type of vaccines we find chickenpox.

Viral vector vaccines

In this case a fragment of the introduced pathogen is used with harmless viral vectors, which are used to transport a specific fragment of the pathogen's DNA. The harmless virus serves as transport (vector) to introduce the pathogenic virus protein into the body. The Ebola vaccine is based on this methodology.

mRNA vaccines

It uses the genetic material of the virus, the instructions for making virus-specific proteins. In this type of vaccine, both DNA and mRNA can be used. The mRNA is something temporary that is destroyed in a matter of hours (low stability), so it remains in our body only the time necessary to express the protein against which we are going to generate immunity.

Vaccines against COVID-19

Given the pandemic situation that has been with us for more than two years, different vaccines have been developed using 2 of the previous methodologies: mRNA and viral vectors.

Currently 3 vaccines stand out worldwide (Pfizer, Moderna and J & J).

J&J: Viral vector vaccine

The virus used to transport the SARS-CoV-2 virus fragment is a adenoviruses similar to the virus that causes the common cold, but to which important parts of the viral genome have been removed so that it cannot replicate in our body, so that it cannot infect and therefore cannot cause the common cold.

The fragment that we incorporated into the adenovirus is what is really specific to each vaccine. In this case, the fragment that interests us has to do with SARS-CoV-2, more specifically with the fragment encoding spike protein which is what SARS-CoV-2 uses to enter our cells and infect us.

When we get the J&J vaccine, the adenovirus with the virus fragment enters the cells of our body and the cells "infected" by this harmless adenovirus synthesize the SARS-CoV-2 spike protein, allowing our immune system to generate antibodies against that body. stranger and thus acquiring immunity.

J&J: viral vector vaccine
Source: Mayo Clinic

Pfizer and Moderna: mRNA Vaccine

In this case, instead of introducing a fragment of the genetic material of SARS-CoV-2, we will introduce the mRNA that encodes the information to express the spike protein. Our cellular machinery will read that mRNA, that is, those instructions to generate the spike protein against which our body will produce antibodies.

If we remember the central dogma of molecular biology, mRNA is the form of the genetic content that gives rise to proteins. Therefore, the method by which we obtain immunity against SARS-CoV-2 is very similar to that of the J&J vaccine but "skipping a step" from the central dogma of molecular biology.

Vaccines of genetic material consist of a specific set of instructions that are inserted into our cells to manufacture the specific harmless proteins that we want so that the immune system can recognize it and induce the immune response.

We could say that these vaccines are like cooking recipes that give us instructions to manufacture the harmless spike protein in our body and thus generate antibodies against that foreign body that we have generated following the instructions of the viral mRNA.

Pfizer and Moderna: mRNA vaccine
Source: Mayo Clinic

Why some people have side effects to vaccines?

COVID-19 vaccines, like many other vaccines, have local reactions such as pain at the injection site and systemic symptoms such as fatigue, fever, chills, and myalgia. However, there is great interindividual variability when we talk about the reaction suffered after being vaccinated against COVID-19.

A scientific study has been carried out to elucidate which genetic variants are associated with this variability. The three main vaccines (Pfizer, Moderna and J&J) have been analyzed. However, because the sample size for J&J was too low in this study, it was excluded from the analysis.

The scientific study reveals that HLA-A*03:01 (HLA: encodes the cell surface proteins responsible for the regulation of the immune system) is the strongest genetic association for people who received the Pfizer vaccine and suffered extreme difficulties in carrying out their daily routine after vaccination against COVID-19. In addition, this variant was also associated with strong side effects in people who received the Moderna vaccine, but the association was much less clear than for the Pfizer vaccine.

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