COVID-19 mRNA vaccines may provide lower immunity to SARS-CoV-2 virus strains

The year 2020 was defined by the COVID-19 pandemic, but it was also a time of remarkable scientific discoveries.

The vaccines were developed in less than a year with the application of mRNA technology, with a 95% efficacy rate in preventing mortality and severe SARS-CoV-2 infection, exceeding the efficacy rate (50%) set by the Office Food and Drug Administration (FDA) for approval.

However, with the advent of new variants of COVID-19 – 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 mRNA vaccines in their current forms against these new variants.

New mutations of SARS- CoV-2

The SARS-CoV-2 virus, like many viruses, invades cells. Because viruses cannot reproduce on their own, they use cellular mechanisms to make copies of their RNA genome.

What sets the SARS-CoV-2 apart is that it has “corrective” equipment for correcting errors during reproduction. For this reason, SARS-CoV-2 appeared to mutate rarely.

In a study conducted in July 2020, viral samples were sequenced and showed an average of 7.23 mutations, which is low compared to the high mutation rates typically displayed by RNA viruses.

In 2020, the most common coronavirus variant was the D614G mutation in the spike protein gene. A study conducted in December 2020 shows that strains that have this variant, can infect cells more easily than the original SARS-CoV-2 virus. However, some scientists argue that it is too early to say how this variant formed the pandemic.

The B.1.1.7 variant

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

This variant was named B.1.1.7 and has several mutations in the spike protein, including the N501Y mutation. Modeling data show that the variant may be 50% more contagious than previous variants.

Since its discovery, the B.1.1.7 variant, has been reported in other parts of the world. The Centers for Disease Control and Prevention (CDC) is currently documenting 981 cases in 37 states.

A CDC modeling study suggests that variant B.1.1.7 will become the dominant variant of COVID-19 in the United States by March of this year.

Variant B.1.351

The B.1.351 variant was first discovered in Nelson Mandela Bay, South Africa, in October 2020. While the CDC reports that this variant originated independently of the B.1.1.7 variant, it shares some common spice protein mutations.

One of them is E484K, which could escape the antibodies, possibly reducing the effectiveness of the vaccines.

Recent reports indicate that experimental vaccines developed by Novavax and Johnson & Johnson may not perform as well against this variant as B.1.1.7.

Based on a study that has not yet been evaluated, it has been suggested that the AstraZeneca-Oxford vaccine is less effective against this variant and thus the vaccination process in South Africa has stopped.

The variant P.1

The CDC reports that variant P.1, was detected in four Brazilian travelers in Japan. It has three mutations in the spike protein: K417N, E484K and N501Y. The variant is reported to be more contagious and possibly more capable of bypassing the immune system.

In early January, a study reported the appearance of variant P.1 in Manaus, Brazil, where it caused a wave of recurrences. In addition, a February article in The Lancet ,reported that the P.1 variant had reached a high of 42% in Manaus, Brazil.

There are no clinical trial data on how mRNA vaccines respond to new variants. However, a new study shows that mRNA vaccines in their current form, could be less effective in developing a sustained immune response. The results were published in the journal Nature .

Studying the neutralizing effect of vaccines

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

The mRNA vaccines trigger the immune system to produce neutralizing antibodies in the receptor binding region of the spike protein. This is an important region that allows SARS-CoV-2 to enter cells.

The researchers evaluated the number of memory B cells present after vaccination. Memory B cells are markers of immune memory, which is important for the body’s ability to recognize the spike protein and be protected against SARS-CoV-2.

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

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

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 site of the spike protein. Almost identical antibodies were produced in either one person receiving the Moderna vaccine or the Pfizer-BioNTech vaccine.

Variations affect antibody levels

The researchers also studied the usefulness of blood plasma in people vaccinated against the new variants.

The researchers modified retroviruses to express one of the 10 mutations in the spike protein. These included three mutations – N501Y, E484K and K417N – or a combination of all three in the protein spike.

The results showed a one to three-fold reduction in the pseudovirus neutralizing capacity when the E484K, N501Y, K417N mutations or a combination of the three were present.

Of the 17 most potent antibodies tested, 14 had the lowest neutralizing activity against the mutated pseudovirus.

Updated treatments are required

The authors write that, similar to the common cold coronavirus variants of HCoV-229E that cause the common cold, the new variants of SARS-CoV-2 could become resistant to the neutralizing antibodies produced by vaccination or previous infection.

“Thus, it is possible that these mutations will reduce the effectiveness of natural immunity and the immunity developed by the vaccine.”

The authors suggest the need for periodic updates of treatments and vaccines for COVID-19 to keep pace with a rapidly evolving virus, according to the data.

Both Pfizer-BioNTech and Moderna are currently working on enhancement targets targeting variant B.1.351. Moderna has also announced upcoming pre-clinical studies and a phase 1 trial to study the effectiveness of additional booster shots.