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The results help explain why vaccinated people are at low risk during the delta rise
Although the infections this summer led to a surge in infections that resulted in thousands of hospitalizations and deaths, the delta variant of the virus that causes COVID-19 isn’t doing particularly well at it, according to a study by Washington University researchers bypassing the antibodies produced by vaccination St. Louis Medical School.
The researchers analyzed a number of antibodies generated by humans in response to the Pfizer COVID-19 vaccine and found that Delta was unable to bypass all but one of the antibodies they tested. Other variants of concern, such as beta, prevented several of the antibodies from recognizing and neutralizing them.
The results, published Aug. 16 in the journal Immunity, help explain why vaccinated people largely escaped the worst of the delta surge.
In previous studies, co-senior author Ali Ellebedy, PhD, Associate Professor of Pathology and Immunology, Medicine, and Molecular Microbiology had shown that both natural infections and vaccinations trigger persistent antibody production. But the length of the antibody response is only one aspect of protection. The width also counts. An ideal antibody response includes a diverse set of antibodies with the flexibility to recognize many, slightly different variants of the virus. Width gives resilience. Even if some antibodies lose the ability to recognize a new variant, other antibodies in the arsenal should be able to neutralize them.
“The fact that Delta has overtaken other variants does not mean that it is more resistant to our antibodies compared to other variants,” said co-senior author Jacco Boon, PhD, Associate Professor of Medicine, Molecular Microbiology and Pathology and Immunology . “The ability of a variant to spread is the sum of many factors. Resistance to antibodies is only one factor. Another is how well the variant replicates. A variant that replicates better is likely to spread faster, regardless of its ability to evade our immune response. So Delta goes up, yes, but there is no evidence that it is better at overcoming vaccine-induced immunity compared to other variants. “
To assess the breadth of the antibody response to SARS-CoV-2, the virus that causes COVID-19, Ellebedy and colleagues – including co-first authors Aaron Schmitz, PhD, a research specialist; Jackson S. Turner, PhD, lecturer in pathology and immunology; and Zhuoming Liu, PhD, an employee scientist – extracted antibody-producing cells from three people who had received the Pfizer vaccine. They grew the cells in the laboratory and received from them a set of 13 antibodies targeting the original strain that circulated last year.
The researchers tested the antibodies against four questionable variants: alpha, beta, gamma and delta. Twelve of the 13 recognized alpha and delta, eight recognized all four variants, and one recognized none of the four variants.
Scientists measure the usefulness of an antibody by its ability to prevent viruses from infecting and killing cells in a shell. It is believed that so-called neutralizing antibodies that prevent infection are stronger than antibodies that recognize the virus but cannot block infection, although both neutralizing and non-neutralizing antibodies help the body’s defenses.
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, three neutralized Alpha and Delta, and only one neutralized all four variants.
“Given the vaccination, Delta is a relatively weak virus,” Ellebedy said. “If we had a variant that was more resistant than Beta, but spread as easily as Delta, we would have more problems.”
The antibody that neutralized all four questionable variants – as well as three other variants tested separately – was named 2C08. In animal studies, 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 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 around 20% of people infected or vaccinated with SARS-CoV-2 develop antibodies that recognize the same site of the virus that 2C08 is targeting. In addition, very few virus variants (0.008%) carry mutations that allow them to escape antibodies that target this site.
“This antibody is not unique to the person we got it from,” said Ellebedy. “Several antibodies have been reported in the literature that target this area; at least one is in development as a COVID-19 therapy. Similar antibodies were raised by people infected in Italy, infected in China, and vaccinated in New York. So it’s not limited to people with particular backgrounds or ethnicities; it is not just produced by vaccination or infection. Lots of people make this antibody, which is great because it’s very strong and it neutralizes any variant we’ve 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 HHSN272201810, AI134907 and 5T32CA00009547, and contract numbers HHSN272201800149C, and contract numbers HHSN2722018000149C, and contract numbers HHSN2722018000149C, and contract numbers HHSN272201800149C, and contract numbers HHSN27200040000149C, and contract numbers HHSN2722018000149C, and contract numbers HHSN2722018000149C, and contract numbers HHSN2722018000149C, and contract numbers HHSN20100622018C947, and contract numbers HHSN20100622018C947, and contract numbers HHSN272201800149C, and contract numbers HHSN20100622018149C; the Children’s Discovery Institute, grant number PDII2018702; the Sealy & Smith Foundation; Kleberg 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 supported in part by the National Center for Advancing Translational Sciences, Grant Number UL1 TR002345.
The 1,700 faculty physicians at Washington University School of Medicine are also the medical staff for the Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, teaching, and patient care and consistently ranks among the best medical schools in the country according to the US News & World Report. The School of Medicine is affiliated with BJC HealthCare through its affiliation with Barnes-Jewish and St. Louis Children’s Hospital.