Monkeys resist coronavirus reinfection; six DNA vaccines show promise in animal studies

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Six rhesus macaque monkeys were resistant to reinfection following exposure to novel coronavirus. Compared with nose, the lungs had very less virus when challenged. In another study, the researchers tested six prototype DNA vaccines that showed good protection in rhesus macaques.

Evidence from studies carried out on rhesus macaque monkeys suggest that once infected with novel coronavirus, the animals may be protected against reinfection. Though early, this is an encouraging news that vaccines when developed may be able to elicit immune response — humoral and cellular immune responses — to protect individuals from infection. The team led by Dan H. Barouch from Harvard Medical School in Boston, Massachusetts published the results in the journal Science.

In total, nine adult rhesus macaques (6-12 years old) were exposed to two different doses of the virus. The researchers found high levels of virus in the lungs and nose (nasal swabs). While the virus cleared by day 10 in the lungs, they persisted for as long as 28 days in the nose.

The researchers next evaluated different immune response by animals that were infected by the virus. They found that all nine animals developed binding antibody responses to the spike protein of virus and neutralising antibody responses too. In addition, antibody responses of multiple subclasses were found.  

On being challenged

On day 35 following initial viral infection, all the nine monkeys were re-exposed or challenged with the same three doses of the virus. Compared with three monkeys that were not earlier infected with the virus, all the nine animals that were challenged showed very less virus in the lungs on day one and no virus on subsequent days. In the case of the nose, the viral load was higher than in lungs but lower than when exposed for the first time (to induce infection). The viral load in the nose after the challenge showed “rapid decline”.  

“Little or no clinical disease was observed in the animals following re-challenge,” they write. What that indicates is that all the nine monkeys mounted an antibody response to the second dose of the virus, suggesting that immune systems could successfully eliminate the virus and protect the animals.

While there is currently no data available in humans suggesting that those have been infected are protected from re-infection, leading to the WHO to caution against using immunity passport while lifting lockdowns, the results from the animals are reassuring. “In this study, we demonstrate that SARS-CoV-2 infection in rhesus macaques provided protective efficacy against rechallenge,” they write.

“However, it is critical to emphasize that there are important differences between SARS-CoV-2 infection in macaques and humans, with many parameters still yet to be defined in both species, and thus our data should be interpreted cautiously,” they caution.  

Testing DNA vaccines

In another paper, also published in Science, the team led by Dr. Barouch immunised 35 adult rhesus macaques (6-12 years old) with six different DNA prototype vaccines. The animals were first immunised with two doses of 5 mg NDA vaccines at weeks 0 and three. At week five, the researchers observed spike protein binding antibodies and neutralising antibodies. The amount of neutralising antibodies found in the vaccinated monkeys was comparable with the amount seen in a cohort of nine monkeys that had recovered from novel coronavirus infection and 27 human convalescent plasma.

All the monkeys were challenged at week six, which is three weeks after the booster dose. No viral RNA could be found in the plasma of the animals, and the animals exhibited only “mild clinical symptoms”. The vaccine was able to elicit robust protection in the lungs than in the nose. And eight of the 25 vaccinated animals did not have detectable virus either in the lungs or in the nose at any timepoint when exposed to the virus following vaccination.

“Protection was likely not sterilising but instead appeared to be mediated by rapid immunologic control following challenge,” they write.

“Our data suggest that vaccine protection against SARS-CoV-2 in macaques is feasible,” they note. There was a “dramatic reduction” of viral replication in both the upper and lower respiratory tract with the optimal vaccines.

They say that is possible to protect against lower respiratory tract disease compared with upper respiratory tract disease. This is exactly what was seen in the case of the Oxford University vaccine trial results on monkeys too; the monkeys did not develop pneumonia but were infected with the virus in the upper respiratory tract.  

In the present study, optimal protection was achieved with the full-length S immunogen in both the upper and lower respiratory tracts and reduced protection when the vaccine contained soluble constructs and smaller fragments.   

Published in The Hindu on May 21, 2020