mRNA vaccines may provide lower immunity to new SARS-CoV-2 variants

  • A small study finds that people showed a robust immune response that targets the spike protein, after receiving either the Pfizer-BioNTech or the Moderna vaccine.
  • Mutations associated with the new variants first found in the United Kingdom, South Africa, and Brazil decreased the number of neutralizing antibodies in the blood.
  • mRNA vaccines and other COVID treatments may need to be periodically updated to keep up with the evolving virus.

The year 2020 was defined by a pandemic, but it was also a time of extraordinary scientific breakthroughs.

Vaccines were developed in less than a year using mRNA technology with a 95% efficacy rate in preventing COVID mortality and severe infection, exceeding the 50% efficacy standard set by the Food and Drug Administration (FDA) for approval.

However, with the emergence of new COVID variants — B.1.1.7, B.1.351, and P.1 — there is concern that these vaccines will not be as effective.

A new study evaluates the effectiveness of the mRNA vaccines in their current forms against these new variants.

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New coronavirus mutations

The coronavirus, like many viruses, “hijacks” cells. Because viruses cannot replicate by themselves, they take over cellular machinery to make copies of the RNA genome.

What sets SARS-CoV-2 apart is that it comes equipped with a “proofreading” mechanism to correct errors during replication. For this reason, SARS-CoV-2 appeared to mutate rarely.

A July 2020 study sequenced viral samples and an average of 7.23 mutations, which is low compared with high mutation rates typically exhibited by RNA viruses.

Last year, the most prevalent coronavirus strain had a D614G mutation on the spike protein gene. A December 2020 study found that D614G’s ability to help the spike protein infect more cells outperformed other existing mutations, making the virus relatively stable.

Because of this stability, mRNA vaccines that prepare the immune system to target the spike protein were expected to neutralize the virus.

The B.1.1.7 variant

Through the COVID-19 Genomics UK Consortium, the U.K. became a world leader in sequencing SARS-CoV-2, and its work helped discover a new strain of the coronavirus.

This strain was labeled B.1.1.7 and has several mutations on the spike protein, including the N501Y mutation. This strain is 50% more infectious than other variants.

Since its discovery, the B.1.1.7 strain has been reported in other places worldwide. The Centers for Disease Control and Prevention (CDC) currently document 981 cases in 37 states.

A CDC modeling study suggests the B.1.1.7 variant will become the dominant COVID strain in the United States by March this year.

The B.1.351 variant

The B.1.351 variant was first discovered in Nelson Mandela Bay, South Africa, in October 2020. While the CDC report that this strain arose independently of the B.1.1.7 strain, it does share some spike protein mutations.

One of the spike protein mutations of concern is E484K, which could evade antibodies, possibly lowering the effectiveness of vaccines.

While not mRNA-based, the vaccines created by Novavax and Johnson & Johnson showed to hold up well against the B.1.1.7 strain but not the B.1.351 strain.

Based on a small study that has not been peer-reviewed, the AstraZeneca-Oxford vaccine was suggested to be less effective against this variant, which halted vaccination efforts in South Africa.

The P.1 variant

The CDC say the P.1 variant was reported in four Brazilian travelers in Japan. It has three mutations on the spike protein: K417N, E484K, and N501Y. The variant is said to be more contagious and potentially able to evade the immune system.

In early January, a preprint study reported the P.1 variant in Manaus, Brazil, where it caused a surge of reinfections. Additionally, a February article in The Lancetreported that the P.1 variant had reached a high frequency of 42% in Manaus, Brazil.

There is no clinical trial data on how the mRNA vaccines fare up against the new variants. However, a new study suggests the mRNA vaccines in their current forms could be less effective in producing a durable immune response. The results appear in the journal Nature.

Studying vaccines’ neutralizing effect

The researchers took blood plasma from six people who received the Pfizer-BioNTech vaccine and 14 people who received the Moderna vaccine, to study the immune system’s response to vaccination.

The mRNA vaccines prime the immune system to target the receptor-binding domain of the spike protein. This is an important area that allows SARS-CoV-2 to enter cells.

The researchers assessed the number of B memory cells present after vaccination. B memory cells are indicators of immune memory, which is important in the body’s ability to recognize the spike protein and defend against SARS-CoV-2.

About 6.2 months after vaccination, people’s number of memory B cells was similar to that of someone who recovered from a SARS-CoV-2 infection.

“Thus, mRNA vaccination elicits a robust SARS-CoV-2 RBD-specific B cell memory response that resembles natural infection,” write the authors.

The study also looked at the type of antibodies produced by memory B cells. The researchers found a neutralizing antibody response against the receptor-binding domain of the spike protein. Whether a person received the Moderna or the Pfizer-BioNTech vaccine, nearly identical antibodies were created.

Variants affect antibody levels

The researchers also studied the usefulness of blood plasma in people who were vaccinated against the new strains.

The researchers altered retroviruses to express one of 10 spike protein mutations. These included three mutations — N501Y, E484K, and K417N — or a combination of the three on the spike protein.

Results showed a one- to three-fold decrease in neutralizing the spike protein when the E484K, N501Y, K417N, or a combination of the three mutations was present.

The mutations decreased or eliminated 14 of the 17 monoclonal antibodies that would typically be present in the blood plasma.

Updated treatments needed

The authors write that, similar to the HCoV-229E strain in the common cold, the new strains in SARS-CoV-2 could become resistant to the same treatment over time.

“Thus, it is possible that these mutations and others that emerge in individuals with suboptimal or waning immunity will erode the effectiveness of natural and vaccine elicited immunity.”

The authors suggest the need for periodic updates to COVID treatments and vaccines to keep up with a rapidly evolving virus, based on the data.

Both Pfizer-BioNTech and Moderna are currently working on booster shots that would target the B.1.351 variant. Moderna have also announced upcoming preclinical studies and a phase 1 trial to study the effectiveness of additional booster shots.

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