- 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.
- Antibodies from volunteers were less able to neutralize model viruses that carried the mutations of the variants first identified in the United Kingdom, South Africa, and Brazil.
- mRNA vaccines and other COVID-19 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-19 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-19 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.
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 variant had a D614G mutation in the spike protein gene. A December 2020 study indicates that this variant can infect cells more easily than the original SARS-CoV-2 virus. Yet some scientists argue that it is too early to say how this variant shaped the pandemic.
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 variant of the coronavirus.
This variant was labeled B.1.1.7 and has several mutations in the spike protein, including the N501Y mutation. Modeling data indicate that the variant may be 50% more infectious than previous variants.
Since its discovery, the B.1.1.7 variant 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-19 variant 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 variant arose independently of the B.1.1.7 variant, 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.
Recent reports show that the experimental vaccine candidates created by Novavax and Johnson & Johnson may not perform as well against this variant as they do against B.1.1.7.
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 in 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.
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 produce neutralizing antibodies to 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.
The researchers also studied the usefulness of blood plasma in people who were vaccinated against the new variants.
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 in the spike protein.
Results showed a one- to three-fold decrease in the ability to neutralize the pseudovirus when the E484K, N501Y, K417N, or a combination of the three mutations was present.
Of the 17 most potent antibodies tested, 14 had lower neutralization activity to the mutant pseudovirus.
The authors write that, similar to human coronavirus HCoV-229E variants that can cause the common cold, the new variants of SARS-CoV-2 could become resistant to neutralizing antibodies generated by vaccination or previous infection.
“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-19 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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