Animals who got breathed in nanobodies have less coronavirus particles in their bronchioles (best panel, orange) and are less swollen (magenta). Credit: Nambulli et al., Science Advances
In a paper released today (May 26, 2021) in Science Advances, scientists from the University of Pittsburgh School of Medicine showed that inhalable nanobodies targeting the spike protein of the SARS-CoV-2 coronavirus can prevent and deal with serious COVID-19 in hamsters. This is the first time the nanobodies– which are comparable to monoclonal antibodies but smaller sized in size, more steady, and more affordable to produce– were evaluated for inhalation treatment versus coronavirus infections in a pre-clinical design.
The scientists revealed that low dosages of an aerosolized nanobody called Pittsburgh inhalable Nanobody-21 (PiN-21) secured hamsters from the significant weight reduction normally related to serious SARS-CoV-2 infection and lowered the variety of infectious infection particles in the animals nasal cavities, throats and lungs by a million-fold, compared to placebo treatment with a nanobody that doesnt neutralize the infection.
” By utilizing an inhalation therapy that can be straight administered to the infection site– the breathing system and lungs– we can make treatments more efficient,” stated co-senior author Yi Shi, Ph.D., assistant teacher of cell biology at Pitt. “We are very fired up and motivated by our data recommending that PiN-21 can be highly protective against severe illness and can possibly avoid human-to-human viral transmission.”
Yi Shi, Ph.D., assistant professor of cell biology, University of Pittsburgh School of Medicine. Credit: Yi Shi
Previously, Shi and coworkers discovered a big repertoire of over 8,000 high-affinity SARS-CoV-2 nanobodies. From this repertoire, the researchers picked an ultrapotent nanobody (Nb21) and bioengineered it into a trimeric kind to additional optimize its antiviral activity. The resulting PiN-21 is by far the most powerful antiviral nanobody that has been determined, according to the researchers evaluation of released studies.
When administered intranasally at the time of infection, the experiments showed that PiN-21 was protective. Hamsters in the PiN-21 treatment group did not lose any body weight, unlike the placebo-treated animals who lost up to 16% of their initial body weight after a week of infection. For the average adult human, the rate of the weight-loss would correspond to shedding approximately 20 pounds in a week.
Even more impressively, inhalation of aerosolized nanobodies at an ultra-low dosage decreased the variety of infectious infection particles in the lung tissue by 6-logs (or a million-fold). Animals who received aerosolized PiN-21 nanobodies had milder changes in the lung structure and a lower degree of swelling than those who got the placebo.
Doug Reed, Ph.D., associate professor of immunology, University of Pittsburgh School of Medicine. Credit: Doug Reed
To deliver therapies by means of aerosolization, the researchers needed to overcome several technical challenges– small particle aerosols have to reach deep into the lung, and treatment particles need to be little enough so that they dont clump together and strong enough to endure the severe pressure required to suspend them in the air. PiN-21 nanobodies, which are around four times smaller than normal monoclonal antibodies with incredibly high stability, are completely matched for the job. They also are more affordable to produce and can be produced quickly to promptly adjust to the shape-shifting virus.
” COVID-19 is now a preeminent disease of the 21st century,” stated co-author Doug Reed, Ph.D., associate professor of immunology at Pitt. “Delivering the treatment directly to the lungs can make a huge distinction for our capability to treat it.”
Scientists point out that the vaccines and nanobodies are complementary and do not compete with one another. Vaccines remain the finest tool to stop the virus from spreading out from person to person, however nanobodies will work to treat individuals who currently are ill and those who cant get vaccinated for other medical reasons.
Appealing early preclinical information, combined with the researchers extensive knowledge about quickly recognizing drug-quality nanobodies, recommend that this approach can provide a economical and convenient restorative choice to control the coronavirus pandemic.
” This work is the outcome of specialists in nanobody production, infectious disease, and aerobiology working carefully together. At the University of Pittsburgh Center for Vaccine Research, we dont just discuss concepts, we in fact make them come to life,” stated co-senior author Paul Duprex, Ph.D., the centers director.
Recommendation: 24 May 2021, Science Advances.DOI: 10.1126/ sciadv.abh0319.
Other authors on the manuscript include Sham Nambulli, Ph.D., Natasha Tilston-Lunel, Ph.D., Linda J. Rennick, Ph.D., William Klimstra, Ph.D., all of the Pitt Center for Vaccine Research; Yufei Xiang, M.S., of Pitts Department of Cell Biology; Zhe Sang, M.S., of Pittsburgh-Carnegie Mellon University Program in Computational Biology; and Nicholas Crossland, Ph.D., of Boston University.
This work was supported by the National Institutes of Health (grant # 1R35GM137905-01), a University of Pittsburgh Translational and scientific Science Institute pilot grant, the University of Pittsburgh, the Pitt Center for Vaccine Research, the Commonwealth of Pennsylvania Department of Community and Economic Development, the Richard King Mellon Foundation and the Henry L. Hillman Foundation.
Shi and Xiang are developers on a pending patent associated to this work filed by University of Pittsburgh (no. 63067567, filed on Aug. 28, 2020).
Formerly, Shi and colleagues discovered a large repertoire of over 8,000 high-affinity SARS-CoV-2 nanobodies. From this collection, the scientists picked an ultrapotent nanobody (Nb21) and bioengineered it into a trimeric kind to further maximize its antiviral activity. The resulting PiN-21 is by far the most powerful antiviral nanobody that has been identified, according to the researchers evaluation of published research studies.
Hamsters in the PiN-21 treatment group did not lose any body weight, unlike the placebo-treated animals who lost up to 16% of their initial body weight after a week of infection. PiN-21 nanobodies, which are approximately 4 times smaller than common monoclonal antibodies with exceptionally high stability, are perfectly matched for the task.