COVID-19 vaccine rollout has begun across the world and in many places health care workers and high-risk groups are beginning to receive the shots. This offers hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use require two doses to be effective, which can create problems with logistics and compliance. Now, researchers from Stanford University have managed to construct and test a promising vaccine candidate for COVID-19. What is unique about this vaccine is that it is a single dose one and it does not require a cold-chain for storage or transport. It is also likely to be a cheaper alternative.
This vaccine, detailed in a paper published in ACS Central Science, contains nanoparticles studded with the same proteins that comprise the virus's distinctive surface spikes. In addition to being the reason why these are called coronaviruses, these spikes facilitate infection by fusing to a host cell and creating a passageway for the viral genome to enter and hijack the cell's machinery to produce more viruses. The spikes can also be used as antigens, which means their presence in the body is what can trigger an immune response.
Nanoparticle vaccines balance the effectiveness of viral-based vaccines with the safety and ease-of-production of subunit vaccines. Vaccines that use viruses to deliver the antigen are often more effective than vaccines that contain only isolated parts of a virus. However, they can take longer to produce, need to be refrigerated and are more likely to cause side effects. Nucleic acid vaccines -- like the Pfizer and Moderna mRNA vaccines that have recently been authorized for emergency use by the FDA -- are even faster to produce than nanoparticle vaccines but they are expensive to manufacture and may require multiple doses.
Initial tests in mice suggest that the Stanford nanoparticle vaccine could produce COVID-19 immunity after just one dose. The researchers are also hopeful that it could be stored at room temperature and are investigating whether it could be shipped and stored in a freeze-dried, powder form. By comparison, the vaccines that are farthest along in development in the United States all need to be stored at cold temperatures, ranging from approximately 8 to -70 degrees Celsius (46 to -94 degrees Fahrenheit). The researchers are continuing to improve and fine-tune their vaccine candidate, with the intention of moving it closer to initial clinical trials in humans.
The spike protein from SARS-CoV-2 is quite large. So researchers removed a section of the spike protein near the bottom. Then they combined this shortened spike with nanoparticles of ferritin, an iron-containing protein, which has been previously tested in humans. Then, in collaboration with scientists from the SLAC National Accelerator Laboratory, the researchers used cryo-electron microscopy to get a 3D image of the spike ferritin nanoparticles in order to confirm that they had the proper structure.
They compared their shortened spike nanoparticles to four other potentially useful variations: nanoparticles with full spikes, full spikes or partial spikes without nanoparticles, and a vaccine containing just the section of the spike that binds to cells during infection. Testing the effectiveness of these vaccines against actual SARS-CoV-2 virus would have required the work to be done in a Biosafety Level 3 lab, so the researchers instead used a safer pseudo-coronavirus that was modified to carry SARS-CoV-2's spikes.
The potential effectiveness of each vaccine was tested by monitoring levels of neutralizing antibodies. Antibodies are blood proteins produced in response to antigens; neutralizing antibodies are the specific subset of antibodies that actually act to prevent the virus from invading a host cell. After a single dose, the two nanoparticle vaccine candidates both resulted in neutralizing antibody levels at least twice as high as those seen in people who have had COVID-19, and the shortened spike nanoparticle vaccine produced a significantly higher neutralizing response than the binding spike or the full spike (non-nanoparticle) vaccines. After a second dose, mice that had received the shortened spike nanoparticle vaccine had the highest levels of neutralizing antibodies.
(With inputs from Agencies)
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