COVID-19: mRNA booster vaccine offers best protection against Omicron

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New research suggests a booster dose of an mRNA COVID-19 vaccine can protect well against the Omicron variant. Sven Hoppe/picture alliance via Getty Images
  • A recent study shows that two doses of mRNA (Pfizer-BioNTech or Moderna) and one dose of viral vector (Johnson & Johnson) COVID-19 vaccines were insufficient to produce adequate immunity to a lab-created Omicron variant or pseudovirus.
  • The Omicron pseudovirus infected cells at a higher rate than other pseudovirus variants.
  • The results demonstrated a booster dose of an mRNA COVID-19 vaccine provided the best immune protection from the Omicron pseudovirus.

Since its first detection in South Africa and Botswana in November 2021, the SARS-CoV-2 variant Omicron (B.1.1.529) has spread rapidly globally. Currently, Omicron is the leading variant of concern in the United States, accounting for about 98% of COVID-19 cases in the week ending January 8, 2022.

All viruses, including SARS-CoV-2, constantly change or mutate to form new variants. Mutations of the virus may result in the decline of the variant, while others cause the virus to thrive.

Dr. William Schaffner, professor of infectious diseases at the Vanderbilt University Medical Center in Nashville, provided some background in an MBL interview.

He explained: “When [SARS-CoV-2 viruses] mutate, they can, on occasion, […] create a variant virus that has new characteristics, you might call it a new personality, and the Omicron […] is one of those. Its surface protein compositions are similar to previous variants but a little bit different.”

Dr. Schaffner added: “So when that happens, the vaccines […] designed against the original [SARS-CoV-2] strains produce antibodies that […] [partially match] the surface structure of the Omicron variant. As a consequence, the protection is not as complete.”

There are currently three COVID-19 vaccines available in the U.S. The primary series consists of two doses of an mRNA vaccine (Pfizer-BioNTech or Moderna vaccines) or one dose of a viral vector vaccine (Johnson & Johnson).

The immune response to COVID-19 vaccines may wane over time and as new variants evolve. Boosters can help combat diminishing neutralizing antibody responses, but it is unknown how well current vaccines protect against Omicron.

This led researchers at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard to conduct a study to investigate the effectiveness of the primary series of COVID-19 vaccines and a booster dose of an mRNA vaccine.

They study’s results appear in the journal Cell. The researchers used a laboratory test validated in previous studies called a pseudovirus neutralization assay.

Pseudovirus neutralization assay

The scientists created harmless versions or pseudoviruses of the original strain (wild-type), Delta, and Omicron SARS-CoV-2 viruses. The researchers then used the assay to test blood samples from 239 vaccinated participants (111 with Pfizer-BioNTech, 88 with Moderna, and 40 with Johnson & Johnson).

The study included people residing in Chelsea, MA — an area with a high rate of COVID-19 — and employees of the Massachusetts General Brigham healthcare system. Participants ranged from 18–78 years old, and 63% were female.

The study stratified participants into five groups:

  • people who received the primary vaccination series in the past 3 months and never developed COVID-19 —recently vaccinated
  • people who received the primary vaccination series in the past 6–12 months and never developed COVID-19 —distantly vaccinated
  • people who received the primary vaccination series in the past 6–12 months and developed COVID-19 — distantly vaccinated with infection
  • people who received a booster dose of the Pfizer or Moderna vaccine in the past 3 months and never developed COVID-19 — booster

The researchers measured the neutralizing antibody response of the blood samples from the four participant groups against the wild-type, Delta, and Omicron pseudoviruses. Researchers found a decreased neutralizing antibody response to the Delta and Omicron pseudovirus versus the original variant.

With the Delta pseudovirus, neutralization was slightly reduced in the recently vaccinated, distantly vaccinated with infection, and booster groups, but undetectable in the distantly vaccinated group.

Booster provided best protection

However, only the participants receiving the booster vaccination demonstrated robust Omicron pseudovirus neutralization, while the other groups showed substantial decreases in neutralization capability.

When researchers compared blood samples from the group recently receiving the primary series of the COVID-19 vaccines to those receiving a booster vaccine within the last 3 months, they found that those receiving boosters had a greater scope and cross-reactivity of neutralizing antibody response to the Omicron pseudovirus.

The researchers then tested the pseudoviruses’ ability to infect cells with and without the ACE2 receptors. ACE2 receptors are necessary for cell entry of SARS-CoV-2 in the body.

As expected, none of the pseudoviruses infected cells without ACE2 receptors. In cells with ACE2 receptors, the Omicron pseudovirus infected cells at a four times higher rate than the wild-type and twice the rate of Delta.

Clear message: ‘Get boosted!’

When asked to comment on the results of the study, Dr. Schaffner expressed that the lack of assessment of the role of cell-mediated immunity was a potential limitation, “but certainly [the study offered] a […] very clear explanation on the antibody side of the immune system.”

He elaborated:

“This is an elegant study that […] [develops] some laboratory evidence that helps us explain the behavior of the virus in the real world. It reinforces the notion […] that two doses of the mRNA vaccines, although they elicit good antibody levels, are not very effective in neutralizing the Omicron virus.”

Dr. Schaffner continued: “However, if you get a booster in addition to your two doses, […] you get more antibody, and you get more diverse antibodies with that booster, [which] turned out to be really quite effective, particularly [with] Omicron. They discovered […] that Omicron pseudovirus infected cells in the laboratory much more efficiently […] than did the pseudoviruses with the other variants — [which] helps explain the increased transmissibility of Omicron.”

In a White House press briefing regarding the Omicron variant on January 5, 2022, Dr. Rochelle P. Walensky, director of the Centers for Disease Control and Prevention (CDC), outlines the organisation’s current recommendations.

She states: “Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection. We’re asking everyone to follow these four steps: Get vaccinated and get boosted, if you are eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or looking for greater extra reassurance before you gather with others.”

Dr. Schaeffner added, “The take-home point is clear — get vaccinated [with] the booster when you become eligible immediately. That will provide the best protection.”

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