Recent research from the Washington University School of Medicine in St. Louis suggests that dangerous, new, fast spreading SARS-CoV-2 variants can avoid antibodies that work against the first iteration of the virus that triggered the pandemic in the first place. The researchers are now finding that more antibodies are necessary to neutralize these mutant-derived variants of COVID-19 originating in South Africa, the United Kingdom, and Brazil. Based on recent laboratory experiments, the results were published in the March 4 edition of Nature Medicine and suggest that existing COVID-19 drugs and vaccines may become less potent as the new variants grow in strength and circulation.
In a piece published recently in the Washington University School of Medicine (WUSM) St. Louis News Hub by Tamara Bhandari, Michael S. Diamond, MD, PhD, senior author of the study, reported, “We’re concerned that people whom we’d expect to have a protective level of antibodies because they have had COVID-19 or been vaccinated against it, might not be protected against the new variants.” The investigator continued “There’s wide variation in how much antibody a person produces in response to vaccination or natural infection. Some people produce very high levels, and they would still likely be protected against the new, worrisome variants. But some people, especially older and immunocompromised people, may not make such high levels of antibodies. If the level of antibody needed for protection goes up tenfold, as our data indicate it does, they may not have enough. The concern is that the people who need protection the most are the ones least likely to have it.”
TrialSite provides a brief breakdown of these most recent important findings.
Are the current batch of drugs and vaccines based on the initial spike protein of SARS-CoV-2?
Yes. And viruses mutate continuously, and the vaccines and therapies that have been developed to counter the virus are based on the protein the pathogen uses known as spike that latches onto and penetrates cells. Those infected with SARS-CoV-2 generate the most protective antibodies in response to this spike protein.
Thus, this spike was the focal point of drug and vaccine development for companies such as Pfizer/BioNTech, Moderna and Johnson & Johnson. That is, strong anti-spike antibodies were identified and selected for development into antibody-based drugs targeting SARS-CoV-2.
How do the variants change things?
This winter, as reported by Ms. Bhandari, fast-spreading variants were detected in the UK, South Africa and Brazil as well as elsewhere. These variants happen to carry mutations in the spike genes, which could dilute the impact of the current spike-targeted drugs and vaccines now in use to prevent or treat COVID-19, reports the Washington University School of Medicine in St. Louis News Hub.
What are the most concerning variants?
∙ B.1.1.7 (United Kingdom)
∙ B.1.135 (South Africa)
∙ B.1.1.248 aka P.1. (Brazil)
How did the investigators conduct the test?
Diamond and colleagues, including first author Rita E. Chen (graduate student), tested the ability of the antibodies to neutralize the three virus variants in a laboratory setting, reports Ms. Bhandari.
More specifically, the investigators tested the variants against antibodies in the blood of those who had recovered from COVID-19 or were vaccinated with BNT162b2, Pfizer’s vaccine. Additionally the team further studied these antibodies in the blood of mice, hamsters and monkeys that also were vaccinated with the experimental vaccine for COVID-19 developed at the Washington University School of Medicine, available via nasal administration.
What did the WUSM St. Louis researchers find with COVID-19 vaccines?
They found that the B.1.1.7 (UK) variant could in fact be neutralized with similar levels of antibodies as necessary to neutralize the original pathogen. However, the South Africa and Brazil variants needed from 3.5 to 10 times more antibody for neutralization.
What about monoclonal antibodies?
These “mass-produced replicas of individual antibodies” have shown real promise at neutralizing the original virus. However, based on a series of tests here, WUSM discovered that the monoclonal antibodies in some cases were completely ineffective.
The core of the problem—E484K
Yes. While each virus variant, reports Ms. Bhandari, carries multiple mutations in the spike gene, the WUSM team developed a panel of viruses with single mutation enabling them to “…parse out the effect of each mutation.” They found that impacting antibody efficacy in most cases was a single amino acid change in the spike protein. This change is known as E484K.
E484K is identified in both the South African and Brazilian variants, however not the UK variant. While B.1.135 represents the South African variant perhaps then its not a surprise that at least one vaccine tested there (AstraZeneca) was less effective in people in South African than in the U.S. where the variant is far less common, at least for now.
What are the true impacts of these variants?
Professor Diamond reports that “We don’t exactly know what the consequences of these new variants are going to be yet.” He continued Antibodies are not the only measure of protection; other elements of the immune system may be able to compensate for increased resistance to antibodies. That’s going to be determined over time, epidemiologically, as we see what happens as these variants spread. Will we see reinfections? Will we see vaccines lose efficacy and drug resistance emerge? I hope not. But it’s clear that we will need to continually screen antibodies to make sure they’re still working as new variants arise and spread and potentially adjust our vaccine and antibody-treatment strategies.”
Who is on the research team?
In addition to Professor Diamond, the co-corresponding author includes Ali Ellebedy, PhD, assistant professor of pathology & immunology, of medicine, and of molecular microbiology at Washington University; and co-corresponding author Pei-Yong Shi, PhD, and co-first author Xianwen Zhang, PhD, of the University of Texas Medical Branch. Other authors can be seen at the source.
Who funded this study?
This study was supported by the National Institutes of Health (NIH), contract and grant numbers 75N93019C00062, 75N93019C00051, 75N93019C00074, HHSN272201400006C, HHSN272201400008C, R01AI157155, U01AI151810, R01AI142759, R01AI134907, R01 AI145617, UL1 TR001439, P30AR073752, U01AI141990, F30AI152327 and 5T32CA009547; the Defense Advanced Research Project Agency, grant number HR001117S0019; the Dolly Parton COVID-19 Research Fund at Vanderbilt University; the Mercatus Center at George Mason University; the Future Insight Prize from Merck KGaA; the Helen Hay Whitney Foundation; the Sealy & Smith Foundation; the Kleberg Foundation; the John S. Dunn Foundation; the Amon G. Carter Foundation; the Gilson Longenbaugh Foundation; the Summerfield Robert Foundation; the American College of Gastroenterology; the EPA Cephalosporin Early Career and Teaching Fellowship; and Townsend-Jeantet Charitable Trust. This study used samples obtained from Washington University School of Medicine’s COVID-19 biorepository, which is supported by the Foundation for Barnes-Jewish Hospital; the Siteman Cancer Center, grant number P30 CA091842 from the National Cancer Institute of the NIH; and the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR002345 from the National Center for Advancing Translational Sciences of the NIH.
Call to Action: Follow the link to the source study results in Nature Medicine.