COVID-19 vaccine antibodies weaker vs. Delta/Kappa viral variants

Antibodies induced by currently available mRNA vaccines can still neutralize the Delta and Kappa variants of the SARS-CoV-2 virus, but do so at a reduced potency, according to a report published in the New England Journal of Medicine.

The Delta variant, first identified in India and previously known as B.1.617.2, is now dominant in the United States. The Kappa variant, previously B.1.617.1, was also first identified in India.

Compared with the Washington strain that arrived in the United States last year, vaccine-induced antibodies are 2.9 times less able to neutralize Delta and 6.8 fold less able to neutralize Kappa. Still, researchers concluded that the antibodies induced by mRNA vaccines will be strong enough in many people and protective immunity is “most likely retained” against Delta and Kappa.

The results, based on laboratory assays with live SARS-CoV-2 virus, come from a collaboration between scientists at Emory, Stanford, St. Jude and the National Institute of Allergy and Infectious Diseases. The results for the Kappa variant results in the NEJM paper were first posted as a preprint.

The results are generally reassuring for people who had COVID-19 early in the pandemic, or have been vaccinated already. However, the “correlates of protection,” or the levels of antibodies necessary to fight off the coronavirus, have not been formally established for the mRNA vaccines. Also, antibodies are not the only source of vaccine- or infection-induced protection against SARS-CoV-2; T cells provide some antiviral activity.

“These findings provide some reassurance that these vaccines do generate a broad antibody response that can block emerging variants, like the Delta and Kappa variants. However, we still do not have a good idea on whether these variants can escape T cell responses,” says Emory virologist Mehul Suthar, PhD, senior author on the NEJM report and assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center. Suthar’s laboratory is based at Yerkes National Primate Research Center.

From vaccinated people, samples were obtained up to 7 weeks after immunization, so it is possible that natural decay of antibodies could combine with reduced potency against variants to open up vulnerability as more time elapses after vaccination. For this report, researchers obtained blood samples from 24 people who had recovered from COVID-19 in 2020, 15 people who had received the mRNA-1273 Moderna vaccine and from 10 people who had received the Pfizer–BioNTech vaccine.

The Delta and Kappa variants both contain mutations in the SARS-CoV-2 spike protein that diminish the ability of previous infection- or vaccine-induced antibodies to bind and neutralize the virus. However, when looking at the effect of mutations on the virus’ behavior, enhanced spread is somewhat independent from the ability to escape antibodies.

Suthar notes that the Delta variant seems to have spread widely in many countries because of enhanced infectivity, likely due to increased processing of the viral spike protein and its greater ability to bind to the host ACE2 receptor. Independently, SARS-CoV-2 continues to spread and mutate, with the potential for other variants to escape immune pressure.

The first author of the NEJM report is postdoctoral fellow Venkata Viswanadh Edara, PhD. To test neutralizing antibodies, Edara and other researchers in Suthar’s laboratory use a live virus assay, which is considered to more accurately reflect the cellular context of antibodies as they interact with infectious virus in culture. Live virus assays are conducted under Biosafety Level 3 conditions, in contrast with pseudovirus assays, which mix SARS-CoV-2 genes into other viruses, and can be performed more conveniently in the laboratory.

The research was supported by the National Institute of Allergy and Infectious Diseases and National Cancer Institute (U19AI05726617S1 CCHI Immune Memory Supplement, U54CA260563,HHSN272201400004C, 75N93021C00016) and Yerkes National Primate Research Center (P51OD011132).

Support also came fromthe Emory-UGA Center of Excellence for Influenza Research and Surveillance, the Emory Executive Vice President for Health Affairs Synergy Fund, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, the Oliver S. and Jennie R. Donaldson Charitable Trust and Woodruff Health Sciences Center’s COVID-Catalyst-I3 Funds and 2020 COVID-19 CURE Award.