Single Injection, Broad Protection

Vaccine generates robust immune responses against SARS-CoV-2 variants

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This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education, and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

In the three months since Johnson & Johnson’s COVID-19 vaccine was granted an emergency use authorization from the U.S. Food and Drug Administration, more than 10 million Americans have received the vaccine, according to the U.S. Centers for Disease Control and Prevention.

The single-dose viral vector vaccine, developed in collaboration with Dan Barouch, the William Bosworth Castle Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, was authorized for use based on clinical trial data showing strong clinical efficacy against symptomatic COVID-19 in the United States, Latin America, and South Africa.

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In a new study published June 9 as an accelerated article in Nature, Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess, and colleagues report on the antibody and cellular immune responses in a group of 20 participants generated by the Ad26.COV2.S vaccine against both the original SARS-CoV-2 viral strain and variants of concern.

The team found that the J&J vaccine induced immune responses against all viral variants.

“The concern is whether SARS-CoV-2 variants may reduce the efficacy of current vaccines that were designed to protect against the original SARS-CoV-2 strain at the beginning of the pandemic,” said Barouch, senior author of the study and co-lead of the vaccine working group of the Massachusetts Consortium on Pathogen Readiness (MassCPR).

“These findings therefore have important implications for vaccine protection against SARS-CoV-2 variants of concern.”

To explore the immune response triggered by the vaccine, Barouch and colleagues administered one or two doses to the 20 volunteers, ages 18 to 55.

All of the individuals in this small group were part of a larger multicenter, randomized, double-blind, placebo-controlled phase 1/2a study to evaluate the vaccine at various doses and schedules.

The researchers then used multiple methods to assess antibody and cellular immune responses against the original viral strain (WA1/2020) and against several viral variants first identified in South Africa (B.1.351 or beta), the United Kingdom (B.1.1.7 or alpha), Brazil (P.1 or gamma) and the U.S. (CAL.20C or epsilon).

The analysis showed that, when compared with antibody responses against the original viral strain, participants had drops in levels of neutralizing antibodies against the beta and gamma variants.

However, two other protective responses—non-neutralizing antibody responses and T cell responses—were either minimally impacted or not impacted by SARS-CoV-2 variants.

In other words, the participants’ immune systems retained some of their ability to counter the viral variants even when their levels of neutralizing antibodies dropped.

These findings may help explain the vaccine’s efficacy, demonstrated in phase 3 clinical trials, protection that likely stems from the presence of non-neutralizing antibodies and/or T cell responses, the team said.

The results from the phase 3 trials, published on April 12 in The New England Journal of Medicine, showed that the vaccine offered strong protection against symptomatic COVID-19 in South Africa and in Brazil where most sequenced COVID-19 cases were caused by variants.

“Although the mechanistic correlates of protection for COVID-19 are not yet known, the vaccine’s robust protective efficacy in these regions raises the possibility that non-neutralizing antibodies and/or T cell responses may also contribute to protection,” said Barouch, who is also a member of the Ragon Institute of MGH, MIT, and Harvard.

“Alternatively, it is possible that low levels of neutralizing antibodies are sufficient for protection against COVID-19.”

This work was supported in part by Janssen Vaccines & Prevention B.V.; the Ragon Institute; the Massachusetts Consortium on Pathogen Readiness; the Musk Foundation; the National Institutes of Health (grants CA260476, AI007151, and AI152296); the Burroughs Wellcome Fund Postdoctoral Enrichment Program; the Howard Hughes Medical Institute’s Hanna H. Gray Fellows Program; the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority (transaction agreement HHSO100201700018C).

Barouch is a co-inventor on related vaccine patents. Please see the publication for a complete list of competing interests.

Adapted from a Beth Israel Deaconess news release.