The recent detection of mutations in the SARS-CoV-2 coronavirus that causes the current covid-19 pandemic is generating some uncertainty regarding the effectiveness of the vaccines used in the current vaccination campaign. Will they still be effective? Before answering, we need to reflect on a series of questions.
How to detect a mutation
Mutations are changes in the sequence of genetic material with respect to the original sequence (Wild-type, wild). In this case, it would be the sequence found in the first virus isolates from humans initially infected in Wuhan (China), which was published for the entire scientific community.
Mutations are detected by sequencing. This technique allows the genetic material to be read as in a code that appears in television series (ACUGGCCCUUACG…). Thus, until completing the approximately 30,000 letters (nucleotides), since coronaviruses have a single RNA fragment (ribonucleic acid) of between 26 to 32 Kb.
Therefore, to detect mutations, the complete sequence must be read and compared with that of the virus of origin. This implies that there must be constant monitoring of the virus sequence by specialized laboratories.
Not all mutations are the same
RNA viruses undergo mutations as a result of failures that occur when they replicate and copy their own genetic material. They are relatively frequent errors. Therefore, we can foresee that many other mutations will appear.
However, thanks to previous studies, for example in human immunodeficiency virus (HIV), it is known that most mutations in viruses are negative. This is what is known as a decrease in the fitness of the virus (the ability to carry out all its processes to complete an infective cycle).
That is, most mutations do not produce significant changes or are detrimental to the virus. However, a very small percentage can produce an improvement in viral fitness, making it more effective in some essential respect. For example, infective capacity (greater transmission) or pathogenic capacity (greater virulence).
On the other hand, it must be considered that a single mutation, unless it produces a drastic change in the behavior of the virus (possible but very unlikely), is not considered to originate a new variant or strain, but there are several mutations necessary. That is why we have been slow to hear the existence of new variants, such as those detected in the United Kingdom or in Africa.
How do current vaccines work?
Both the Pfizer and Moderna vaccines are gene vaccines that are based on messenger RNA (mRNA). It contains the information necessary to produce part of the spike protein of the SARS-CoV-2 coronavirus.
The spike protein is the one that binds to the receptor in our cells (mainly ACE2, for angiotensin-converting enzyme 2), allowing the entry of the virus and, therefore, infection.
This vaccine uses a coating with lipids so that the mRNA enters the cells of the immune system, called “antigen presenting cells”, mainly the dendritic cells.
Synthetically produced mRNA looks like our RNA. This means that it does not activate the machinery of our innate immune system too much, because if it were not like that, it would degrade it when it detects that it is a viral RNA. In this way, the mRNA goes unnoticed and ends up producing the spike protein inside the cells.
Said protein will be fragmented into smaller pieces (peptides) that bind to class I and class II histocompatibility molecules. They are taught on the surface of dendritic cells (presentation) to two types of lymphocytes, the so-called CD8 + T lymphocytes and CD4 + T lymphocytes, respectively.
At this time, the adaptive immune response is activated and cytotoxic lymphocytes and the much desired antibody-producing cells (plasma cells differentiated from specifically activated B lymphocytes) will be produced, among other actors.
Antibodies can block the entry of the virus into cells and act as tags that help other components and cells of the immune system to eliminate the virus (neutralization).
Cytotoxic lymphocytes are capable of eliminating cells infected by the virus, preventing new progeny from being produced, but at the cost of causing some damage to our own cells.
Will I be protected against new mutations?
As mentioned, the spike protein mRNA vaccine causes the immune system to detect different fragments of it (peptides). Therefore, if a mutation occurs, it is most likely that it affects one of the fragments of that protein and not all.
That is, most of the specific immune response would not be affected. Although it is true that there are immunodominant peptides that generate more powerful immune responses, and it is possible that if the mutation affects an immunodominant peptide it will have a greater impact.
Let’s be optimistic and think that in a short period of time it is unlikely that a variant of the virus will appear against which we are not protected with current vaccines. If this were to happen, thanks to the relatively simple production process of RNA-based vaccines, it could quickly and efficiently go on to produce mRNA as it appears in the new variant (mutated). This would imply a new vaccination campaign.
Narcisa Martínez Quiles, Professor at the University. Area: Immunology. Others: Microbiology, Cellular and Molecular Biology., Complutense University of Madrid
This article was originally published on The Conversation. Read the original.
