Macaques show protective immunity against SARS-CoV-2 after infection or after vaccine

Two new studies in macaques offer hope that humans could develop protective immunity against SARS-CoV-2, either as the result of a natural infection or by way of a vaccine. While there are differences between SARS-CoV-2 infection in macaques and humans, these findings – some of the first to show that non-human primates can develop protective immunity to SARS-CoV-2 – are promising in light of the ongoing efforts around the world to develop a vaccine and antibody treatments for COVID-19. An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure; there is currently no data on whether humans are protected from re-exposure in this way. Earlier this year, research investigating cynomolgus macaques found these animals to be promising models for testing COVID-19 therapeutics. Here, in two new studies in rhesus macaques, researchers explored whether initial exposure to SARS-CoV-2 protected against reinfection and whether vaccination protected against infection, respectively. In a macaque model of SARS-CoV-2 infection they developed, and which recapitulated certain aspects of human SARS-CoV-2 infection, Abishek Chandrashekar, Ralph Baric, Dan Barouch and colleagues tested whether 9 adult animals who had cleared the virus were immune to viral re-challenge 35 days later. All 9 animals showed little to no symptoms after re-challenge and exhibited immune responses that protected against the second infection (given at the same doses as the first). Additional research will be required to define the durability of natural immunity shown here, the authors note. “Rigorous clinical studies will be required to determine whether SARS-CoV-2 infection effectively protects against SARS-CoV-2 re-exposure in humans,” they say.

In a separate study including many of the same researchers, and led by Jingyou Yu, the researchers designed prototypes of SARS-CoV-2 DNA vaccine candidates that expressed six different forms of the SARS-CoV-2 spike protein, which is used by the virus to bind and invade human cells. The vaccine candidates provide DNA that allows host cells to make the spike protein so as to generate antibody responses to it. Yu and colleagues vaccinated 35 adult macaques with these vaccines, in initial rounds and boost immunizations. These animals exhibited similar humoral and cellular immune responses to the macaques recovering from first-round infection in the study by Chandrashekar

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, Yu and colleagues report. And critically, when these vaccinated macaques were infected intranasally with SARS-CoV-2 six weeks later, they exhibited levels of antibodies in their blood sufficient to neutralize the virus in two weeks’ time. These levels were similar to those seen in humans recovering from SARS-CoV-2 infection, the authors say. This also demonstrates protective immunity in the macaques, likely mediated by an immune system response, which was also the case in Chandrashekar

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. Yu and colleagues say that further research will be needed to determine the optimal vaccine platforms for a SARS-CoV-2 vaccine for humans, but that their work could accelerate the development of these vaccines.

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