COVID-19 Vaccine Induced Antibodies Effective Against Delta Variant – Washington University School of Medicine in St. Louis



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Findings help explain why people vaccinated at low risk during delta surge

Matt Miller

Although it caused an upsurge in infections this summer that resulted in thousands of hospitalizations and deaths, the delta variant of the virus that causes COVID-19 is not particularly effective at evading antibodies generated by vaccination, according to a study by researchers at the University of Washington. Saint-Louis medical school.

The researchers analyzed a panel of antibodies generated by people in response to the Pfizer COVID-19 vaccine and found that delta was unable to escape all but one of the antibodies they tested. Other worrisome variants, such as beta, avoided recognition and neutralization by many of the antibodies.

The findings, published Aug. 16 in the journal Immunity, help explain why those vaccinated largely escaped the worst of the Delta wave.

In previous studies, lead co-author Ali Ellebedy, PhD, associate professor of pathology and immunology, medicine and molecular microbiology, had shown that natural infection and vaccination induce long-lasting antibody production. But the duration of the antibody response is only one aspect of protection. Width matters too. An ideal antibody response includes a diverse set of antibodies with the flexibility to recognize many slightly different variants of the virus. The width gives resilience. Even if some antibodies lose the ability to recognize a new variant, other antibodies in the arsenal should still be able to neutralize it.

“Just because delta has outperformed other variants does not mean that it is more resistant to our antibodies compared to other variants,” said co-lead author Jacco Boon, PhD, associate professor of medicine, of molecular microbiology and pathology and immunology. “The ability of a variant to spread is the sum of many factors. Antibody resistance is only one factor. Another is the quality of the replication of the variant. A variant that replicates better is likely to spread faster, regardless of its ability to evade our immune response. So the delta is increasing, yes, but there is no evidence that it is better at overcoming vaccine-induced immunity compared to other variants. “

To assess the extent of the antibody response to SARS-CoV-2, the virus that causes COVID-19, Ellebedy and colleagues – including co-lead authors Aaron Schmitz, PhD, research specialist; Jackson S. Turner, PhD, instructor in pathology and immunology; and Zhuoming Liu, PhD, scientific staff member – extracted antibody-producing cells from three people who had received the Pfizer vaccine. They cultured the cells in the lab and obtained a set of 13 antibodies targeting the original strain that began circulating last year.

The researchers tested the antibodies against four variants of concern: alpha, beta, gamma, and delta. Twelve of the 13 recognized alpha and delta, eight recognized all four variants and one did not recognize any of the four variants.

Scientists evaluate the usefulness of an antibody by its ability to prevent the virus from infecting and killing cells in a box. So-called neutralizing antibodies that prevent infection are believed to be more powerful than antibodies that recognize the virus but cannot block infection, although both neutralizing and non-neutralizing antibodies help defend the body.

The researchers found that five of the 13 antibodies neutralized the original strain. When they tested the neutralizing antibodies against the new variants, all five antibodies neutralized delta, all three neutralized alpha and delta, and only one neutralized all four variants.

“In the face of vaccination, delta is a relatively weak virus,” Ellebedy said. “If we had a more resilient variant like beta but that spread as easily as delta, we would have more problems. “

The antibody that neutralized the four variants of concern – along with three additional variants tested separately – was called 2C08. In animal experiments, 2C08 also protected hamsters from diseases caused by each variant tested: the original variant, delta, and an imitation of beta.

Some people may have antibodies just as strong as 2C08 that protect them against SARS-CoV-2 and its many variants, Ellebedy said. Using publicly available databases, the researchers found that about 20% of people infected or vaccinated against SARS-CoV-2 create antibodies that recognize the same location on the virus that is targeted by 2C08. In addition, very few viral variants (0.008%) carry mutations that allow them to escape antibodies targeting this location.

“This antibody is not unique to the person we got it from,” Ellebedy said. “Multiple antibodies targeting this area have been described in the literature; at least one is in development as a COVID-19 therapy. Similar antibodies have been generated by people infected in Italy and people infected in China and people vaccinated in New York. So it’s not limited to people of certain origins or ethnicities; it is not generated only by vaccination or by infection. Lots of people make this antibody which is great because it is very potent and neutralizes every variant that we have tested. “

Schmitz AJ, Turner JS, Liu Z, Zhou JQ, Aziati IS, Chen RE, Joshi A, Bricker TL, Darling TL, Adelsberg DC, Altomare CG, Alsoussi WB, Case JB, VanBlargan LA, Lei T, Thapa M, Amanat F , Jeevan T, Fabrizio T, O’Halloran JA, Shi PY, Presti RM, Webby RJ, Krammer F, Whelan SPJ, Bajic G, Diamond MS, Boon ACM, Ellebedy AH. A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants. Immunity. August 16, 2021. DOI: 10.1016 / j.immuni.2021.08.013

This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), grant numbers U01AI141990, U01AI150747, R01AI157155, R01AI118938, U01AI151810, AI134907 and 5T32CA009547 and contract numbers 4N00004HSN27000, H201004NHSN27000, H201004NHSN27000; the NIH, grant number UL1TR001439 and contract number 75N93019C00062; the Children’s Discovery Institute, grant number PDII2018702; the Sealy & Smith Foundation; Kléber Foundation; the John S. Dunn Foundation; the Amon G. Carter Foundation; the Gilson Longenbaugh Foundation; the Summerfield Robert Foundation; and a Helen Hay Whitney Postdoctoral Fellowship. The SARS-CoV-2 vaccine study was partially supported by the National Center for Advancing Translational Sciences, grant number UL1 TR002345.

The 1,700 physicians on the Washington University School of Medicine faculty are also on the medical staff at Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, education, and patient care, consistently ranking among the nation’s top medical schools by US News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s Hospitals, the School of Medicine is linked with BJC HealthCare.

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