By Gary Evans, Medical Writer

Current vaccines are holding against an emerging array of highly transmissible SARS-COV-2 variant strains, but researchers are warning that a somewhat literal “arms race” has begun between immunization science and relentless evolution.

For now, the remarkable 94%-95% efficacy of the two available COVID-19 vaccines creates a buffer, meaning some degradation of effectiveness would still keep people out of the hospital and the morgue — a truism often applied to flu shots. The rise of these variant strains gives healthcare workers another important reason to get immunized, although some still are hesitant or outright refusing vaccination. (See related story in this issue.)

The Food and Drug Administration (FDA) has granted emergency use authorizations (EUA) to two messenger RNA vaccines for COVID-19 in the United States: one from Pfizer-BioNTech and one from Moderna.

A flurry of pre-publication, non-peer-reviewed research on the efficacy of immunization against the variant strains has been released, including a study that revealed some diminished efficacy of the Moderna vaccine against the variant B.1.351 strain that has emerged in South Africa. The same study revealed the Moderna vaccine was fully effective against another major strain of concern, United Kingdom (UK) B.1.1.7.1

“For the South African strain, we still see a very high level of antibody, but it is lower than the traditional strain and B.1.1.7,” Moderna CEO Stéphane Bancel said in a recent interview. “We believe our vaccine will be protective in the short term. What is unknowable right now is what will happen in six months, in 12 months, especially to the elderly because they have a weakened immune system, and the immunity might go down over time.”2

Out of an “abundance of caution,” the company will test a single-dose booster shot targeting the South African strain. The vaccine will use the same mRNA platform of the approved vaccines, but will genetically target the B.1.351 strain. Working with the FDA, the booster could be deployed this spring if there are signs of waning immunity in the elderly. “We cannot fall behind this virus,” Bancel said. “We just wanted to be cautious, not for now, but for the future.”

As this issue went to press, the Centers for Disease Control and Prevention (CDC) announced the first documented U.S. case of the South African B.1.351 variant had been detected in South Carolina.

“At this time, we have no evidence that infections by this variant cause more severe disease,” the CDC stated. “Like the U.K. and Brazilian variants, preliminary data suggests this variant may spread more easily and quickly than other variants.”3

Few other details were released, but more variants are expected to be detected because the CDC has expanded National SARS-CoV-2 Strain Surveillance.

“We continue working with national reference laboratories, state health departments, and researchers from around the country to gather sequence data and increase use of genomic sequencing data in response to this pandemic,” the CDC said.

“Part of the challenge of recognizing these variants is a lack of public health laboratory infrastructure in order to do the surveillance,” Rochelle Walensky, MD, MPH, the new director of the CDC, said in a recent interview. “Part of the president’s budget is to bolster that dramatically. The work is already being done to create those connections with industry, academic, and public health labs to make sure we can [identify] these variants across the country.”4

Formerly an infectious diseases physician at Harvard Medical School and Massachusetts General Hospital, Walensky took the helm of the beleaguered agency at the height of the pandemic as an appointee of the Biden administration.

“Even if vaccines in the labs don’t appear as robust [against variants] as the initial strain, we will probably still end up with quite a good vaccine,” she noted. “Almost no vaccine we have is 95% [effective], so before we panic [and say] ‘Should I get the vaccine if it is not going to work against the variants?’ It’s going to work against the variants. Will it be 95%? Maybe. Will it be 70%? Maybe. Our flu vaccines are not that effective every year and we still get them. I’m optimistic about how these variants are going to go. I could be wrong, and we find variants for which the vaccine is less potent.”

U.K. Strain Becoming Predominant

Fortunately, both vaccines have shown efficacy against the U.K. B.1.1.7 variant, which the CDC has projected will be the predominant strain in the United States by March.5 Researchers in England are warning in addition to be being highly transmissible, there is “a realistic possibility” the variant may cause infections with higher rates of mortality.6

Initially, the U.K. variant was thought to be no more virulent than the original, wild strain on a “one-to-one” basis, but the fact it is more transmissible was expected to lead to overall deaths in any case, said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases.

“The one in the U.K. appears to have a greater degree of transmissibility — about twice as much as the wild type original virus,” he said at a recent press conference.7 “If you have a virus that is more transmissible, you get more hospitalizations. When you get more hospitalizations, you ultimately are going to get more deaths.”

As of Jan. 25 (based on limited genetic sequencing), there were 293 cases of COVID-19 in 24 states caused by the U.K. B.1.1.7 variant, according to the CDC.8

“We need to be much better at sequencing this virus,” Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in a recent interview. “When [these variants] come up, what we need to identify initially is to see whether or not the sera that are obtained from people who are immunized with these mRNA vaccines neutralize the virus. That is what you need to know.”9

A recent pre-print study revealed both vaccines sufficiently protected against the U.K. and South African strains, but researchers warned that encoded genetic mutations can diminish efficacy to some degree.

“Taken together, the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy,” the authors concluded.10

The authors of another study examined whether unvaccinated patients who were convalescing or completely recovered from COVID-19 infection were immune to the South African variant.11

“Of the 44 that they tested, 22 didn’t neutralize the virus,” Offit said. “There were a handful of sera that did neutralize the virus completely. Those were obtained from people who had more severe disease and had higher titers and neutralizing antibodies. The vaccine may induce higher, longer-lasting titers than from people who are convalescent, which could have broader range of neutralizing titers just because they had different levels of disease.”

In addition to vaccines, emerging variants threaten to undermine monoclonal antibody treatments for COVID-19. “Since monoclonal antibodies bind to a very specific part of the virus, when there is a mutation there it has a much greater chance of obliterating the efficacy of a monoclonal antibody,” Fauci said. “We are seeing in the much more concerning mutations that are in South Africa and in some respect Brazil — which is similar, it is having an effect on the monoclonal antibodies.”

First Case of Brazil Strain in United States

The first U.S. case of the Brazil P.1 variant, which has spread rapidly in areas of that country, was detected in a traveler returning from Brazil to the Twin Cities metro area in Minnesota on Jan. 25, state health officials announced.12

“With the new lab information showing the case to be the Brazil P.1 variant, epidemiologists are re-interviewing the person to obtain more details about the illness, travel, and contacts,” the health department said.

The Brazil variant contains 17 unique mutations, including three in the receptor binding domain of the spike protein. “There is evidence to suggest that some of the mutations in the P.1 variant may affect its transmissibility and antigenic profile, which may affect the ability of antibodies generated through a previous natural infection or through vaccination to recognize and neutralize the virus,” the CDC reports.13

Over time, as SARS-COV-2 persists and globally circulates, treatments and vaccines might require augmenting to meet the threat of variant mutations.

“If we ever have to modify the vaccine, it is not something that is a very onerous thing,” Fauci said. “We can do that given the platforms we have. What we are likely to see is a diminution of the vaccine-induced antibodies. That does not mean that the vaccines will not be effective.”

A key message is the variants make vaccination even more important, as mutations will continue to arise if SARS-CoV-2 runs unchecked through large populations.

“It is all the more reason why we should be vaccinating as many people as we possibly can,” Fauci said. “Viruses don’t mutate unless they replicate. If you can suppress that by a very good vaccine campaign, then we can avoid this deleterious effect of mutations.”

REFERENCES

  1. Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv 2021;2021.01.25.427948. [Preprint].
  2. CNBC. Transcript: Moderna CEO Stéphane Bancel Speaks with CNBC’s “Squawk Box.” Jan. 25, 2021. https://www.cnbc.com/2021/01/25/cnbc-transcript-moderna-ceo-stephane-bancel-speaks-with-cnbcs-squawk-box-today.html
  3. Centers for Disease Control and Prevention. South Carolina detects first US cases associated with variant first detected in South Africa. Jan. 28, 2021. https://www.cdc.gov/media/releases/2021/s0128-sc-detects-COVID-variant.html
  4. JAMA Network. Coronavirus update with CDC Director Rochelle Walensky. Conversations with Dr. Bauchner. Jan. 19, 2021. https://www.youtube.com/watch?v=TSopzX_uZ5Q&ab_channel=JAMANetwork
  5. Galloway SE, Paul P, MacCannell DR, et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020-January 12, 2021. MMWR Morb Mortal Wkly Rep 2021;70:95-99.
  6. Horby P, Huntley C, Davies N, et al. NERVTAG note on B.1.1.7 severity. Jan. 21, 2021. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/955239/NERVTAG_paper_on_variant_of_concern__VOC__B.1.1.7.pdf
  7. The White House. Press briefing by Press Secretary Jen Psaki, Jan. 21, 2021. https://www.whitehouse.gov/briefing-room/press-briefings/2021/01/21/press-briefing-by-press-secretary-jen-psaki-january-21-2021/
  8. Centers for Disease Control and Prevention. US COVID-19 Cases Caused by Variants. Updated Jan. 31, 2021. https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html
  9. JAMA Network. Coronavirus vaccine update with Paul Offit and Robert Wachter. Conversations with Dr. Bauchner. Jan 19, 2021. https://www.youtube.com/watch?v=XrHbBolmmqc&ab_channel=JAMANetwork
  10. Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv 2021;2021.01.15.426911. [Preprint].
  11. Wibmer CK, Ayres F, Hermanus T, et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv 2021;2021.01.18.427166. doi: 10.1101/2021.01.18.427166. [Preprint].
  12. Minnesota Department of Health. MDH lab testing confirms nation’s first known COVID-19 case associated with Brazil P.1 variant. Jan. 25, 2021. https://www.health.state.mn.us/news/pressrel/2021/covid012521.html
  13. Centers for Disease Control and Prevention. Emerging SARS-CoV-2 variants. Updated Jan. 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html