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People who have already had COVID-19 may not benefit from a second dose of an mRNA vaccine. APU GOMES/AFP via Getty Images
  • A new study suggests that there is a strong boost to the immunity of everyone who receives the first dose of an mRNA vaccine, including those who have previously had a SARS-CoV-2 infection.
  • However, only people who have never had a SARS-CoV-2 infection appeared to benefit from the second dose.
  • The scientists tracked not only antibody responses to vaccination but also the creation of memory B cells, which provide longer lasting immunity against infection.
  • People who experienced particularly negative side effects from the vaccine — such as fever, headache, and muscle pain — had stronger immune responses.

Clinical trials of the Moderna and Pfizer COVID-19 vaccines have found that they are highly effective at preventing SARS-CoV-2 infections.

Both shots are mRNA vaccines. This is a new technology that uses strands of genetic material called messenger RNA to provide the body’s own cells with instructions to make proteins from the virus.

Although these isolated viral proteins are harmless, they provoke an immune response that provides protection against a subsequent infection with the actual virus.

Previous investigations into how well the immune system responds to mRNA COVID-19 vaccines have mainly focused on the production of antibodies that can neutralize the SARS-CoV-2 virus. However, this is only part of the story.

In response to an infection or vaccination, the body not only produces antibodies but also generates long lived immune cells known as memory B cells.

If the number of neutralizing antibodies in the bloodstream declines and they do not combat a new infection, memory B cells can step up to produce more antibody-producing cells.

Memory B cells are also crucial for generating variations on existing antibodies that can neutralize emerging strains of a virus. This is through a process known as somatic hypermutation.

After a person recovers from a SARS-CoV-2 infection, their antibodies and memory B cells can provide protection against reinfection for at least 8 months.

However, researchers know much less about the ability of mRNA vaccines to stimulate the production of memory B cells and the longer lasting, flexible immunity to new strains that they can confer.

“Memory B cells are a strong predictor of future antibody responses, which is why it’s vital to measure B cell responses to these vaccines,” says Prof. E. John Wherry, Ph.D., director of the Penn Institute for Immunology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants,” he adds.

It has also been unclear whether or not a person who has recovered from COVID-19 needs both doses of the vaccine to obtain optimum immunity against reinfection.

If such people require only one dose, healthcare professionals could, in theory, use the spare doses to protect other people if vaccine supplies are limited.

To address these questions, Prof. Wherry and team recruited 44 healthy volunteers. Of these, 33 people were “SARS-CoV-2 naïve.” This means that they had never had the virus. The remaining 11 people had recovered from a previous SARS-CoV-2 infection.

All the participants were about to have their first dose of either the Pfizer or the Moderna vaccine.

The researchers collected blood samples from them at the start of the study, 2 weeks after their first dose, on the day of their second dose, and 1 week after their second dose.

The antibody levels of the SARS-CoV-2-naïve participants did not peak until after the second dose.

This was particularly true for antibodies capable of neutralizing the B.1.351 strain of the virus, which is a “variant of concern” that scientists first identified in South Africa.

It was also the case for neutralizing antibodies for the D614G mutation, which researchers believe makes the virus more transmissible.

In addition, two key lineages of memory B cell did not peak in the blood of the SARS-CoV-2-naïve participants until after their second dose.

These were the B cells that remember the spike protein, which allows the virus to gain entry into cells, and the receptor binding domain, which is the part of the spike protein that binds to a receptor on the cells.

However, in people who had recovered from a previous SARS-CoV-2 infection, their antibody and memory B cell responses peaked after the first dose of the vaccine.

The research now appears in the journal Science Immunology.

The findings may prove useful for drawing up future vaccination strategies.

“We need to make sure people have the strongest memory B cell responses available,” says Prof. Wherry.

“If circulating antibodies wane over time, our data suggest that durable memory B cells could provide a rapid source of protection against reexposure to COVID-19, including variants,” he adds.

Interestingly, the bodies of SARS-CoV-2-naïve participants who experienced more severe side effects after vaccination — such as fever, headache, fatigue, and muscle pain — tended to mount stronger antibody responses.

Prof. Wherry explains:

“Everyone has good responses to the vaccines. They work to protect people against COVID-19. But for those who may be worried about side effects, they are not necessarily a bad thing — they may actually be an indicator of an even better immune response.”

The authors emphasize that their laboratory-based study was unable to prove that people who have recovered from COVID-19 only need one dose of an mRNA vaccine to optimize their immunity to future SARS-CoV-2 infections.

A large clinical trial would be necessary to assess the efficacy of one or two doses against actual infections.

Another limitation of the study was that the individuals who recovered from the infection did not require hospitalization. Therefore, the results may not be applicable to people who experience more severe infections.

Finally, it is worth noting that all the participants were healthy. Conditions that increase a person’s vulnerability to COVID-19 — such as high blood pressure, obesity, and diabetes — may also affect their immune response to vaccination.

The researchers will extend their research to discover how long the different types of immunity last following vaccination.

They are also looking into the responses of T cells, which are the other wing of the body’s adaptive immune response to pathogens such as viruses.

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