The only thing better than one new study showing positive COVID-19 vaccine results in monkeys is two studies. Two papers, published back-to-back in Science this week are some of the first to show that non-human primates can develop protective immunity to SARS-CoV-2—a finding critical for vaccine and public health strategies.

“The global COVID-19 pandemic has made the development of a vaccine a top biomedical priority, but very little is currently known about protective immunity to the SARS-CoV-2 virus,” said Dan H. Barouch, MD, PhD, professor of medicine, Harvard Medical School, director, Center for Virology and Vaccine Research, BIDMC, and senior author on both studies. “In these two studies, we demonstrate in rhesus macaques that prototype vaccines protected against SARS-CoV-2 infection and that SARS-CoV-2 infection protected against re-exposure.”

Earlier this year, research investigating cynomolgus macaques found these animals to be promising models for testing COVID-19 therapeutics. In order to probe whether infection with SARS-CoV-2 results in protective immunity against re-exposure, researchers developed a macaque model of SARS-CoV-2 infection that recapitulated certain aspects of human SARS-CoV-2 infection.

In the paper, “SARS-CoV-2 infection protects against rechallenge in rhesus macaques”, the group tested whether nine adult animals who had cleared the virus were immune to viral re-challenge 35 days later.

After exposing nine adult macaques to the SARS-CoV-2 virus, the researchers monitored viral levels as the animals recovered. All nine animals recovered and developed antibodies against the virus. More than a month after the initial infection, the team re-exposed the rhesus macaques to the virus. Upon second exposure, the animals demonstrated near-complete protection against the virus. These data suggest natural protective immunity against COVID-19 in this model.

The authors wrote that “macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia.” Following initial viral clearance, they explained, animals were rechallenged with SARS-CoV-2 and “showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection.”

All nine 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 noted. “Rigorous clinical studies will be required to determine whether SARS-CoV-2 infection effectively protects against SARS-CoV-2 re-exposure in humans,” they said.

In a separate study that included many of the same researchers, titled “DNA vaccine protection against SARS-CoV-2 in rhesus macaques,” the team developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques (25 adult rhesus macaques with the investigational vaccines and 10 animals received a sham control).

Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2.

Importantly, 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. Follow-up testing revealed dramatically lower viral loads in vaccinated animals compared to the control group. Eight of the 25 vaccinated animals demonstrated no detectable virus at any point following exposure to the virus, and the other animals showed low levels of virus.

Moreover, higher antibody levels were linked to lower viral loads, suggesting that neutralizing antibodies may serve as a correlate of protection and may prove useful as a benchmark in clinical testing SARS-CoV-2 vaccines.

“Our findings increase optimism that the development of COVID-19 vaccines will be possible,” said Barouch. “Further research will be needed to address the important questions about the length of protection, as well as the optimal vaccine platforms for a SARS-CoV-2 vaccine for humans.

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