Let’s answer some questions about Covid-19 vaccines: mutations of the genome, infertility, efficacy and more
Can the Covid vaccine modify our genome?
No. The central dogma of biology says that DNA is copied into RNA and RNA translated into protein. If DNA were a culinary book, RNA would be a copy of the recipe we are interested in and the protein the final dish that we would create. It never happens that RNA interferes with DNA except for some exceptions (that we will see shortly), which however have nothing to do with the Covid-19 vaccine.
A necessary requirement for an RNA molecule to interfere with our genome is that it is transported from the cytoplasm to the cell nucleus. If we think of the cell as a bank, the RNA would queue with customers, while DNA would be safe in the vault. The cell nucleus is an isolated compartment with pores that impose a physical limit on the size of particles that can enter freely. Once a stretch of DNA is copied into RNA, this is transported into the cytoplasm, where it is translated into a protein, while there is no physiological circumstance in which the RNA is transported back into the nucleus. Only some proteins can follow the reverse path: this is because they have a nuclear localization sequence (NLS), which we could define as the entrance ticket to a museum: if you have it, you enter, if you do not have it, you stay outside. This sequence allows them to attach to other proteins (importins) whose role is to help them reach the nucleus. Since NLS is a sequence of amino acids (the constituents of proteins), by definition it cannot be contained in an RNA molecule, which is instead formed by nucleotides.
How does RNA from the vaccine get into cells? RNA is contained in lipidic spheres which, once injected into the body, fuse with the cell membrane (also lipidic), releasing it in the cytoplasm. Lacking associated proteins that present NLS (in the vaccine there is only RNA and no protein), once in the cytoplasm, the RNA will never reach the nucleus, therefore its fate is sealed: for a few hours it will be exploited to produce the protein encoded (the Spike protein of the SARS-CoV-2 virus), after which it will be destroyed.
Now let’s spend a few words on the rare instances where RNA can interfere with the genome. This can only happen when RNA is copied into DNA. This step (the opposite of what the central dogma of molecular biology dictates) is known as reverse transcription, and is performed by an enzyme called reverse transcriptase. Reverse transcription is performed by a few genetic entities: retroviruses, telomeres and retrotransposons.
- Retroviruses are viruses with an RNA genome that, once a cell is infected, reverse transcribe their genome by creating a copy in DNA, which then integrates permanently into the human genome. In this way, the host cell is no longer able to recognize it and will unknowingly start producing new viral particles that will infect other cells. This is the mechanism of action of the HIV virus. What would happen if there was a viral reverse transcriptase in a cell, in which the vaccine RNA was also found? Nothing would happen, because reverse transcriptases are unable to take an RNA molecule at random to reverse-transcribe it: for example, they require a specific RNA sequence to trigger the reaction.
- Telomeres are the ends of human chromosomes. These are repeated sequences of nucleotides that need constant maintenance to avoid excessive consumption (the chromosome ends are delicate and can be seen as the corners of a school notebook). The shortening of telomeres leads to cellular aging and when they are too short, the cell dies. A reverse transcriptase called TERT is responsible for maintaining telomeres. The process is quite complicated, but we can limit ourselves to mentioning that TERT uses an RNA template to produce the repeating sequence of DNA which will then be added to the ends of the telomeres to prevent their shortening. Could TERT exploit the vaccine’s RNA to modify the genome? No, because the RNA template used by TERT is specific and its functioning is dictated by the nucleotide sequence, which cannot vary. The RNA of the vaccine is too large and has a totally different sequence, which makes it incompatible with TERT.
- Retrotransposons are the most abundant component of the genome (they make up more than half of it) and are divided into several categories, all of which are irrelevant for RNA vaccines. If it were up to me, I wouldn’t go into details, but unfortunately fake news leverage technicalities, so I have to say a few words about it. There are 4 types of retrotransposons: SINEs (short interspersed nuclear elements), LINEs (long interspersed nuclear elements), human endogenous retroviruses (HERVs) and processed pseudogenes. Let’s make it short. SINEs code for short RNA molecules and, in order to function, they need a reverse transcriptase which is encoded by LINEs. Thanks to this collaboration, some (very few) LINEs and SINEs can copy each other and the new copies integrate into other parts of the genome (very rarely this has biological consequences). HERVs are remnants of retroviruses that integrated into the human genome between 25 and 150 million years ago and lost their infectivity. The pseudogenes have also been integrated into the genome after reverse transcription and, like HERVs, are inert. It is evident that the only doubt can be linked to the reverse transcriptases encoded by the LINEs, but if we remember that these only work with the SINEs, we can rest assured. Always reminding us that the RNA of the vaccine will never meet the endogenous reverse transcriptases (TERT, or LINEs, or whatever they are) because it is unable to enter the cell nucleus.
Can the Covid vaccine cause infertility?
Vaccines against Covid-19 have been given to tens of thousands of people during clinical trials and infertility has not been a problem, neither for men nor for women. Despite this, the vaccine has not been specifically studied in pregnant women. Before doing this, studies using animal models must be conducted to investigate potential developmental and reproductive toxicity (DART). Pfizer’s DART studies are currently underway and results expected in the near future, while Moderna’s are already available and have not detected any problems in pregnant animals.
However, there is a (unfounded) rumor that antibodies against the Spike protein (which we develop after the vaccine) also target a protein found in the placenta of pregnant women, syncithin-1, which promotes embryo implantation: given the similarity with the Spike protein, it has been hypothesized that antibodies against it may also mistakenly affect syncithin-1, causing infertility. However, there are no data to support this hypothesis, since syncytin-1 and the Spike protein are sufficiently different (only a small part of them are similar) to minimize the probability that the antibodies developed against the latter are able to attack the first. Confirming this, twenty-three women became pregnant after participating in Pfizer’s vaccine clinical trial. There was only one reported case of terminated pregnancy in a woman belonging to the control/placebo group, which means she had not even received the vaccine. So why is the vaccine not recommended for pregnant women? Because the effects on pregnancy have not yet been extensively studied, and until all risks are ruled out, it’s better to be on the safe side. One last consideration: if the antibodies against the Spike protein were really able to recognize and attack syncytin-1, then all people who got sick with Covid-19 (who therefore naturally developed antibodies against the Spike protein) would risk infertility, which is definitely not the case.
Are Pfizer and Moderna RNA vaccines effective enough?
For those who received two doses of the vaccine, Pfizer reported 95% efficacy, while Moderna 94.1%. This means that 19 out of 20 people will not get Covid after being vaccinated. The efficacy values are in line with, if not better than, those of other vaccines. Here are some examples: the seasonal flu vaccine is about 44% effective (changing every year, it is not always possible to predict the viral strain and this significantly lowers the effectiveness), the one against chickenpox 90% and the trivalent against measles, mumps and rubella (MMR) 97%. Why is one dose not enough? Pfizer indicated that the effectiveness of its vaccine after one dose is 52% while Moderna 80.2%. That’s why two doses are recommended.
Is it true that some people have died during clinical trials of Covid vaccines?
Yes, but no fatalities were related to the vaccine. 6 deaths in the study population, 2 in the vaccinated group and 4 in the control (unvaccinated) group were noted in Pfizer’s briefing document. In the information document of Moderna, 13 deaths were noted, 6 in the vaccinated group and 7 in the control group. These numbers are in line with the mortality of the population, so nothing to worry about.
Could the Covid vaccine cause anaphylactic shock?
Unfortunately it can happen (as with any other vaccination), albeit with a very low probability. So far there have been some cases of allergy that required hospitalization, but all the subjects have then quickly recovered. Individuals who have a history of anaphylaxis to any other vaccine or injectable therapy (such as intramuscular, intravenous, or subcutaneous injections) can receive the Covid-19 vaccine, but must first be informed by their medical practitioner about the risk of developing a severe allergic reaction, to weigh it with the benefits of vaccination (for example if the subject is at risk). They must also be monitored for 30 minutes after vaccination.