New Research Explains Why Vaccinated People at Low Risk During COVID Delta Variant Surge

Vaccines do not ward off every infection, but they greatly reduce the risk.

Antibodies elicited by COVID-19 vaccination effective against Delta variant

Despite sparking a spate of infections this summer that has led to thousands of hospitalizations and deaths, the delta variant of the virus that causes COVID-19 is not particularly good at evading the antibodies generated by vaccination, according to a study. from researchers at Washington University School of Medicine in St. Louis.

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

The findings, published Aug. 16 in the journal Immunity, help explain why vaccinated people have largely escaped the worst delta rise.

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

Cherry Grimmett, a BJC HealthCare security officer, will receive her first dose of the Pfizer COVID-19 vaccine in December 2020. Researchers at Washington University School of Medicine in St. Louis have found that the delta variant of the virus that carries COVID-19 19 is largely unable to evade vaccine-induced antibodies. The findings help explain why vaccinated people are at low risk of becoming seriously ill with COVID-19, despite an increase in cases caused by the delta variant. Credit: Matt Miller/Washington University

“The fact that delta has outperformed other variants does not mean 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, independent of its ability to evade our immune response. So delta goes up, yes, but there’s no evidence it’s better at overcoming vaccine-induced immunity compared to other variants.”

To assess the scope 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, an instructor in pathology and immunology; and Zhuoming Liu, PhD, a staff scientist — 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 started 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 recognized none of the four variants.

Scientists judge an antibody’s usefulness by its ability to prevent viruses from infecting and killing cells in a dish. So-called neutralizing antibodies that prevent infection are thought to be more potent than antibodies that recognize the virus but cannot block the infection, although both neutralizing and non-neutralizing antibodies contribute to 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.

“In the light of vaccination, delta is relatively a flaccid virus,” Ellebedy said. “If we had a variant that was more resistant like beta, but spread as easily as delta, we’d have more problems.”

The antibody that neutralized all four variants of concern — as well as three additional variants tested separately — was named 2C08. In animal experiments, 2C08 also protected hamsters against diseases caused by every variant tested: the original variant, delta and a beta mimic.

Some people may have antibodies as potent 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 make antibodies that recognize the same spot on the virus that is targeted by 2C08. In addition, very few virus variants (0.008%) carry mutations that allow them to escape antibodies targeting that site.

“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 is not limited to people of any particular background or ethnicity; it is not generated by vaccination or infection alone. A lot of people make this antibody, which is great because it’s very potent and neutralizes every variant we’ve tested.”

Reference: “A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants” by Aaron J. Schmitz, Jackson S. Turner, Zhuoming Liu, Julian Q. Zhou, Ishmael D. Aziati, Rita E. Chen, Astha Joshi, Traci L. Bricker, Tamarand L. Darling, Daniel C. Adelsberg, Clara G. Altomare, Wafaa B. Alsoussi, James Brett Case, Laura A. VanBlargan, Tingting Lei, Mahima Thapa, Fatima Amanat, Trushar Jeevan, Thomas Fabrizio , Jane A. O’Halloran, Pei-Yong Shi, Rachel M. Presti, Richard J. Webby, Florian Krammer, Sean PJ Whelan, Goran Bajic, Michael S. Diamond, Adrianus CM Boon and Ali H. Ellebedy, Accepted, Immunity .
DOI: 10.1016/j.immuni.2021.08.013