The Infectious Diseases Society of America (IDSA) held a media briefing on January 21, 2021 to discuss the impact of coronavirus disease 2019 (COVID-19) variants in the United States.1

Variant B.1.1.7, a more highly transmissible variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in 22 states across the United States.2 This variant has a total of 17 mutations and higher viral loads of SARS-CoV-2 have been detected on nasopharyngeal swabs.3,4

Variant B.1.351, another highly transmissible variant of SARS-CoV-2 originally identified in South Africa, has not yet been detected in the United States.2


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A recent study in Germany5 assessed the efficacy of Pfizer’s COVID-19 vaccine against the B.1.1.7 variant. Study authors found no biologically significant difference in neutralization activity compared to previous variants, and concluded that “it is very unlikely that the UK variant viruses will escape BNT162b2-mediated protection.”

Moderna conducted in vitro neutralization studies of sera from those trial participants vaccinated with mRNA-1273, Moderna’s COVID-19 vaccine.6 Results showed “no significant impact of neutralizing titers against B.1.1.7” but a “[6]-fold reduction in neutralizing titers was observed [against the] B.1.351 variant.” Moderna has launched a clinical program to boost immunity to emerging variants.

Kathryn M Edwards, MD, Professor of Pediatrics at the Vanderbilt University School of Medicine in Nashville, Tennessee, and Scientific Director of the Vanderbilt Vaccine Research Program, and Mirella Salvatore, MD, Assistant Professor of Medicine and Population Health Sciences at Weill Cornell Medicine in New York City, New York, reviewed what we currently know and what we can expect from theSARS-CoV-2 variants.

Difficulty of Updating Vaccines and Challenges for Regulators

Dr Edwards: mRNA vaccines will be possible and easier to update than protein-based vaccines. That is an advantage of mRNA vaccines. A number of us are thinking about how this could work, and we look to influenza.

Every year, we choose influenza strains to put in the vaccine. When we do that, we have to change the strains a number of times. Then they go into a number of ferrets to look at immune responses and into some people as well. This process is done so efficiently by the FDA and a number of regulators, and the ability to change strains is something we do every year.

As we move forward, we’re using influenza as a model, using the virus strains that are being extensively sequenced, and then we’re trying to predict whether the antibodies generated by the vaccine will neutralize those strains. This process might be slightly harder for other vaccines, but it would be a possibility, as this is what we do with influenza, which is an inactivated vaccine. I think this is possible.

Affect of Vaccine on People Who Had Mild Illness

Dr Edwards: There are variation in immune response, varying by individual. One of the things we’ve been watching closing is what happens to people that has been infected and then get a dose of the vaccine. When people who were mildly infected get a dose of the vaccine, they have robust responses.

Growing Concerns of Global Variants

Dr. Salvatore: The South African variant and the Brazilian variant are still not widespread. They are not detected in the United States. These variants might spread or it might be a failure of our surveillance system.

Our level of worry about a variant is associated with how radically it can change the structure of its spike protein. Some of the variants have more mutations in the receptor binding domain. The fear is that the more mutations you have in that site, the more you decrease the antibody response. Or if you have a lot of mutations, it will change the conformation of the spike protein.

Some of these mutations were tested in a small study and the vaccine still seems to work. A pre-print from the Rockefeller University tested a combination of variants on a small number of patients.7 There is encouraging data but we do see a decrease in the efficacy of the vaccine. We need to follow the studies, but we do not need to panic.

References

1. IDSA media briefing: coronavirus variants. News release. ID Society. January 21, 2021. Accessed January 25, 2021. https://www.idsociety.org/multimedia/videos/idsa-media-briefing-coronavirus-variants/

2. Emergence of SARS-CoV-2 B.1.1.7 lineage – United States, December, 29, 2020 – January 12, 2021. Centers for Disease Control and Prevention. January 15, 2021. Accessed January 25, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm

3. Kidd M, Richter A, Best A, et al. S-variant SARS-CoV-2 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-QPCR. medRxiv. Published online December 27, 2020. doi:10.1101/2020.12.24.20248834

4. Rambaut A, Loman N, Pybus O, et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. Virological. December 8, 2020. Accessed January 25, 2021. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

5. Muik A, Wallisch AK, Sänger B, et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. bioRxiv. Published online January 19, 2021. doi:10.1101/2021.01.18.426984

6. Moderna COVID-19 Vaccine Retains Neutralizing Activity Against Emerging Variants First Identified in the U.K. and the Republic of South Africa. News release. Moderna. January 25, 2021. Accessed January 25, 2021. https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against

7. Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv. Published online January 19, 2021. doi:10.1101/2021.01.15.426911