News & Views: 3 Questions You Will Get About the New mRNA Vaccines

The first COVID-19 vaccines to be approved by the FDA were bound to garner much attention; however, the fact that they employ a technology never before used in a vaccine approved for use in people means even more questions and concerns. Vaccine Education Center staff have been busy answering lots of questions on our dedicated webpage, COVIDVaccineAnswers.org, but we wanted to offer a bit more depth on three questions you are bound to be asked:

1. Can mRNA vaccines alter a person’s DNA?
2. What ingredients are in the new mRNA vaccines?
3. Can a vaccinated person still spread the virus?

You will also likely be asked about the allergic reactions that occurred in a few vaccine recipients in the UK. Please check the “In the journals” section of the newsletter, where Dr. Offit discusses this additional, important topic of interest.

Can mRNA vaccines alter a person’s DNA?

The short answer to this question is “no,” but in and of itself that is not very satisfying, so let’s take a closer look. We can be confident that mRNA vaccines are not able to alter a person’s DNA for three reasons:

1. Location — mRNA is active in the cytoplasm of a cell, whereas DNA is protected in the cell’s nucleus. The mRNA cannot enter the nucleus, so the two nucleic acids are never in the same place in the cell.
2. Process — mRNA is not DNA. So, if a person’s DNA was going to be altered, the RNA would have to be made into DNA. This would require an enzyme called reverse transcriptase. People do not have this enzyme, and only some viruses do. Coronaviruses are not one of them. Viruses in the Coronaviridae family have single-stranded RNA, known as “positive-sense” RNA. This means when coronaviruses enter the cytoplasm, they do not need to be transcribed. Proteins can be made directly from the virus’s positive-sense RNA. In this manner, the mRNA vaccine acts the same way, delivering mRNA to the cytoplasm for direct translation into protein.
   
   Some have suggested that people infected with human immunodeficiency virus (HIV) have reverse transcriptase, and wonder if, therefore, the vaccine could cause changes in their DNA. This is not likely either since HIV infects CD4+ T cells, and the mRNA vaccines are processed by dendritic cells. Likewise, if the presence of reverse transcriptase from a long-term infection allowed for RNA from viruses to alter an infected individual’s DNA, this would have been identified, given the number of people living with HIV.
3. Stability — mRNA is not very stable. Its half-life in human cells is estimated in hours. For purposes of mRNA-based therapies, modifications have been developed to keep the molecule in cells long enough to allow for the therapy to be successful. But even with this, the mRNA will not lead to protein production for more than 10-14 days.

What ingredients are in the new mRNA vaccines?

Because mRNA vaccines rely on a nucleic acid and not production of virus particles or proteins, they have relatively few components compared with more traditional vaccines. The Pfizer vaccine lists four categories of agents, with one to four items in each category:

• mRNA — In the case of COVID-19 vaccines, the mRNA for the SARS-CoV-2 spike protein is the antigen.
• Lipids — Four lipids, that form little water-insoluble particles, are included in the Pfizer vaccine to protect the mRNA:
  • (4-hydroxybutyl) azanediyl)bis(hexane-6,1-diyl) bis (2- hexyldecanoate) — This lipid has been referred to as ALC-0315, and it has a net positive charge, so when mixed with the negatively charged mRNA molecule during production, it helps to form the basis of the particles.
  • 2-[(polyethylene glycol)-2000]-N, N-ditetradecylacetamide — This lipid, ALC-0159, serves to stabilize the particles containing the mRNA.
  • 1,2-distearoyl-sn-glycero-3-phosphocholine — This lipid is found in a variety of foods and is a natural substance, and it also helps with stabilizing the mRNA-containing particles.
  • Cholesterol — Also serves to stabilize the chemical structure of the particles.
• Salts — Four salts are included to ensure that the vaccine’s pH is appropriate for administration:
  • Potassium chloride
  • Monobasic potassium phosphate
  • Sodium chloride (table salt)
  • Dibasic sodium phosphate dihydrate
• Sucrose — More commonly called sugar, this ingredient prevents clumping and sticking of the lipid molecules.

Almost as important as what the vaccines contain is the list of things these vaccines do not contain. Because they do not require growth of or contain virus, no antibiotics or preservatives (thimerosal) are necessary. Likewise, no cell lines are used in their production, so rumors of fetal cells in these vaccines are ill-founded. To note, some of the other COVID-19 vaccines that may be developed use fetal tissues, but the mRNA vaccines do not.

Blood products are also not contained in the mRNA vaccines. One source of confusion related to this was a USA Today article about the use of horseshoe crab blood in the Limulus amebocyte lysate, or LAL, test used to check vaccines and other biological products for endotoxins.

The mRNA vaccines do not contain any proteins, so concerns about egg or gluten allergies are moot.

Likewise, the vaccines do not contain microchips, as widely circulated online. Snopes has addressed this issue if you want to read more or share with patients.

Can a vaccinated person still spread the virus?

Some of the messaging related to the mRNA vaccines and how well they worked in the clinical trials has been lost in translation by the media, leaving people confused about how they might still be able to spread the virus if the vaccine worked. Here is some context for addressing this point of confusion:

• Infection occurs when the virus can reproduce in a person’s body.
• So, if vaccination stops infection, the virus will not reproduce and, therefore, the person won’t be able to spread the virus.
• But, the Pfizer and Moderna studies evaluated “disease” as a marker for infection — meaning they determined who got COVID-19 using a case definition of symptoms. According to briefing documents supplied by the FDA (p. 14) in relation to the Pfizer product, the case definition for a confirmed COVID-19 case was the presence of at least one of the following symptoms and a positive SARS-CoV-2 NAAT [PCR or other approved nucleic acid test] within four days of the symptomatic period:
  • Fever
  • New or increased cough
  • New or increased shortness of breath
  • Chills
  • New or increased muscle pain
  • New loss of taste or smell
  • Sore throat
  • Diarrhea
  • Vomiting
  As such, “efficacy” represents the people who did not have symptoms. This allows for a scenario in which people could have been infected (the virus reproducing), but because of the immunity from the vaccine, the infection was not significant enough to induce symptoms.
  
  Studies on several college campuses are planned for early next year to determine whether vaccinated people could have asymptomatic infection that results in levels of live virus sufficient to spread the virus to others if public health measures are not used. These studies will do contact tracing with people who have been exposed to people who have or have not received the vaccine.

Update: September 16, 2021

While we now know that vaccinated people can be infected with the virus that causes COVID-19 and we know that these individuals have detectable amounts of viral proteins similar to the amounts found in unvaccinated persons early but not late during infection, we continue to wait for data to answer the question of whether vaccinated people who get COVID-19 can spread the virus. It is likely that some previously vaccinated individuals who become infected can spread the virus to others, especially those who get severely ill. However, two caveats are important to understand:

1. Having detectable viral proteins is not the same as having intact, infectious virus particles that can be spread to others and cause them to become ill. We are still waiting for this type of data to emerge.
2. Even if vaccinated people become infected and can spread the virus to others, they are likely to spread significantly less virus than a previously unvaccinated person who becomes infected and they are likely to spread virus for a shorter period of time.