This article is part of Harvard Medical Schoolscontinuing coverageof medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

Since thenovel coronavirusemerged at the end of 2019, scientists around the world, including immunologist Dan Barouch, The William Bosworth Castle Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, have been developing vaccines to protect against COVID-19 and to put an end to the pandemic.

As of November 2020, three pharmaceutical companies released early data showing high rates of protection in phase III human trials for their vaccines, but questions remain about how the body develops and maintains immunity after vaccination or infection.

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In a new paper in the journalNature, Barouch, director of theCenter for Virology and Vaccine Research at Beth Israel Deaconess, and colleagues shed light on the role of antibodies and immune cells inprotectionagainst SARS-CoV-2, the virus that causes COVID-19, in rhesus macaques.

In this study, we define the role of antibodies versus T cells in protection against COVID-19 in monkeys. We reportthat a relatively low antibody titer [the concentration of antibodies in the blood] is needed for protection, said Barouch. Such knowledge willbe important inthe development of next-generation vaccines, antibody-based therapeutics and public health strategies for COVID-19.

Building on previous findings that SARS-CoV-2 infection protects rhesus monkeys from re-exposure, Barouch and colleagues purified and collected antibodies from animals that had recovered from infection.

They administered the antibodies at various concentrations to 12 uninfected macaques and observed that protection against SARS-CoV-2 challenge was dose-dependent.

Animals that received higher amounts of antibodies were protected more completely, while animals that received lower amounts of antibodies were less protected. Similarly, when the researchers administered various concentrations of the purified antibodies to six macaques with active SARS-CoV-2 infection, those given higher doses demonstrated more rapid viral control.

In a second set of experiments, Barouch and colleagues evaluated the role of specific immune cells, CD8+ T cells, in contributing to protection against SARS-CoV-2 infection by removing these cells from animals that had recovered from the virus. Removal of these immune cells left the animals vulnerable to infection after re-exposure to SARS-CoV-2.

Our data define the role of antibodies and T cells in protection against COVID-19 in monkeys.Antibodies alone can protect, including at relatively low levels, but T cells are also helpful if antibody levels are insufficient, said Barouch, who is also a steering committee member of the Ragon Institute of MGH, MIT and Harvard.

Such correlates of protection are important given the recent successful vaccine results from human trials and the likelihood that these and other vaccines will become widely available in the spring. As a result, future vaccines may need to be licensed based on immune correlates rather than clinical efficacy.

Thework was supported by the Ragon Institute, Mark and Lisa Schwartz Foundation, Massachusetts Consortium on Pathogen Readiness, Bill & Melinda Gates Foundation (grant INV-006131), and National Institutes of Health (grants OD024917, AI129797, AI124377, AI128751, AI126603 and CA260476).

The authors declare no financial conflicts of interest. Barouch is a co-inventor on provisional SARS-CoV-2 vaccine patents (62/969,008; 62/994,630).

Adapted from a Beth Israel Deaconess news release.

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Degrees of Protection | Harvard Medical School - Harvard Medical School