Researchers Seek to Detail Nuances of Immunity to SARS-CoV-2

Researchers Seek to Detail Nuances of Immunity to SARS-CoV-2
Illustration of antibodies (y-shaped) responding to a coronavirus infection. Different strains of coronavirus are responsible for diseases such as the common cold, gastroenteritis and SARS (severe acute respiratory syndrome). The new coronavirus SARS-CoV-2 (previously 2019-CoV) emerged in Wuhan, China, in December 2019. The virus causes a mild respiratory illness (Covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells' machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by phagocyte immune cells.

With multiple entities in hot pursuit of developing COVID-19 vaccines, many questions still remain about how the body develops and maintains immunity after vaccination or infection. Now, a group led by Dan Barouch, M.D., Ph.D., at Harvard Medical School is trying to put some of the puzzle pieces into place—findings that may have important implications for the development of SARS-CoV-2 vaccines and immune-based therapeutics.

Barouch, the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, and colleagues, shed light on the role of antibodies and immune cells in protection against SARS-CoV-2 in rhesus macaques. “In this study, we define the role of antibodies versus T cells in protection against COVID-19 in monkeys. We report that a relatively low antibody titer (the concentration of antibodies in the blood) is needed for protection,” said Barouch. “Such knowledge will be important in the development of next-generation vaccines, antibody-based therapeutics, and public health strategies for COVID-19.”

This work is published in Nature, in the article titled, “Correlates of protection against SARS-CoV-2 in rhesus macaques.

First, the team showed that the adoptive transfer of purified IgG from convalescent macaques protects naïve recipient rhesus macaques against SARS-CoV-2 challenge in a dose dependent fashion. 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 the 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 protected less well. 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 the virus by removing these cells from animals that had recovered from SARS-CoV-2 infection. Removal of these immune cells left the animals vulnerable to infection after re-exposure to SARS-CoV-2.

The authors wrote: “Depletion of CD8+ T cells in convalescent animals partially abrogated the protective efficacy of natural immunity against SARS-CoV-2 re-challenge, suggesting the importance of cellular immunity in the context of waning or subprotective antibody titers.”

These data, the authors noted, demonstrate that “relatively low antibody titers are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may also contribute to protection if antibody responses are suboptimal.” They also showed that higher antibody titers are required for therapy of SARS-CoV-2 infection in macaques.

“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. “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.”