Researchers at Stanford are working to develop a single-dose vaccine for SARS-CoV-2 that might potentially be kept at space temperature level.
Prior to the pandemic, the lab of Stanford University biochemist Peter S. Kim focused on establishing vaccines for HIV, Ebola and pandemic influenza. Within days of closing their campus lab space as part of COVID-19 preventative measures, they turned their attention to a vaccine for SARS-CoV-2, the infection that triggers COVID-19 The coronavirus was outside the laboratory’s particular location of expertise, they and their collaborators have managed to construct and test a promising vaccine prospect.
” Our goal is to make a single-shot vaccine that does not need a cold-chain for storage or transport. If we’re successful at doing it well, it needs to be low-cost too,” stated Kim, who is the Virginia and D. K. Ludwig Teacher of Biochemistry. “The target population for our vaccine is low- and middle-income countries.”
Their vaccine, detailed in a paper published on January 5, 2021, in ACS Central Science, includes nanoparticles studded with the exact same proteins that make up the virus’s unique surface area spikes.
Nanoparticle vaccines stabilize the effectiveness of viral-based vaccines with the safety and ease-of-production of subunit vaccines. Vaccines that use viruses to provide the antigen are typically more reliable than vaccines that contain only separated parts of a virus. They can take longer to produce, need to be cooled and are more likely to cause side effects. Nucleic acid vaccines– like the Pfizer and Moderna mRNA vaccines that have actually recently been licensed for emergency usage by the FDA– are even quicker to produce than nanoparticle vaccines but they are expensive to make and might need several doses. Initial tests in mice suggest that the Stanford nanoparticle vaccine might produce COVID-19 immunity after simply one dose.
The scientists are also enthusiastic that it might be stored at space temperature level and are examining whether it could be delivered and kept in a freeze-dried, powder form. By comparison, the vaccines that are farthest along in development in the United States all require to be kept at cold temperature levels, ranging from approximately 8 to -70 degrees Celsius(46 to -94 degrees Fahrenheit).
” This is actually early phase and there is still great deals of work to be done,” said Abigail Powell, a previous postdoctoral scholar in the Kim laboratory and lead author of the paper. “But we think it is a strong starting point for what might be a single-dose vaccine routine that doesn’t depend on utilizing a virus to generate protective antibodies following vaccination.”
The researchers are continuing to enhance and tweak their vaccine prospect, with the intent of moving it closer to initial medical trials in people.
Spikes and nanoparticles
The spike protein from SARS-CoV-2 is rather large, so scientists often formulate abridged versions that are simpler to make and easier to utilize. After carefully examining the spike, Kim and his team picked to eliminate a section near the bottom.
To complete their vaccine, they combined this shortened spike with nanoparticles of ferritin– an iron-containing protein– which has been previously evaluated in humans. Prior to the pandemic, Powell had been working with these nanoparticles to establish an Ebola vaccine.
For the mouse tests, the researchers compared their shortened spike nanoparticles to four other possibly useful variations: nanoparticles with full spikes, complete spikes or partial spikes without nanoparticles, and a vaccine consisting of just the area of the spike that binds to cells throughout infection. Checking the effectiveness of these vaccines versus real SARS-CoV-2 infection would have required the work to be carried out in a Biosafety Level 3 laboratory, so the scientists instead utilized a more secure pseudo-coronavirus that was customized to carry SARS-CoV-2’s spikes.
The researchers determined the potential efficiency of each vaccine by tracking levels of reducing the effects of antibodies. Antibodies are blood proteins produced in reaction 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 led to neutralizing antibody levels at least two times as high as those seen in individuals who have had COVID-19, and the shortened spike nanoparticle vaccine produced a substantially higher reducing the effects of action than the binding spike or the full spike (non-nanoparticle) vaccines. After a second dosage, mice that had gotten the shortened spike nanoparticle vaccine had the greatest levels of neutralizing antibodies.
Recalling at this task, Powell estimates that the time from inception to the very first mouse studies had to do with 4 weeks. “Everybody had a lot of energy and time to devote to the very same scientific problem,” she stated. “It is a very distinct circumstance. I don’t actually anticipate I’ll ever experience that in my profession once again.”
” What’s happened in the past year is really wonderful, in terms of science coming to the fore and being able to produce multiple different vaccines that look like they’re showing efficacy versus this virus,” stated Kim, who is senior author of the paper. “It usually takes a decade to make a vaccine, if you’re even successful.
Although the group’s brand-new vaccine is meant specifically for populations that may have more problem accessing other SARS-CoV-2 vaccines, it is possible, offered the quick development of other vaccine candidates, that it will not be needed to attend to the existing pandemic. In that case, the researchers are prepared to pivot again and pursue a more universal coronavirus vaccine to immunize against SARS-CoV-1, MERS, SARS-CoV-2 and future coronaviruses that are not yet known.
” Vaccines are one of the most extensive accomplishments of biomedical research study. They are an extremely cost-efficient way to protect individuals versus disease and conserve lives,” stated Kim. “This coronavirus vaccine is part of work we’re currently doing– establishing vaccines that are traditionally challenging or difficult to establish, like an HIV vaccine– and I’m thankful that we’re in a circumstance where we could possibly bring something to bear if the world requires it.”
Referral: “A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Reducing The Effects Of Antibody Actions against SARS-CoV-2 in Mice” by Abigail E. Powell, Kaiming Zhang, Mrinmoy Sanyal, Shaogeng Tang, Payton A. Weidenbacher, Shanshan Li, Tho D. Pham, John E. Pak, Wah Chiu and Peter S. Kim, 5 January 2021, ACS Central Science
DOI: 10.1021/ acscentsci.0 c01405
Additional Stanford co-authors include Kaiming Zhang, research scientist in bioengineering; Mrinmoy Sanyal, research scientist in biochemistry; Shaogeng Tang, postdoctoral fellow in biochemistry; Payton Weidenbacher, graduate student in chemistry; Shanshan Li, postdoctoral researchers in bioengineering; Tho Pham, scientific assistant professor in pathology at Stanford Medication (also affiliated with the Stanford Blood Center in Palo Alto); and Wah Chiu, the Wallenberg-Bienenstock Teacher at Stanford and the SLAC National Accelerator Laboratory, and professor of bioengineering and of microbiology and immunology. Kim is a member of Stanford Bio-X, the Maternal & Kid Health Research Institute (MCHRI) and the Wu Tsai Neurosciences Institute, and a faculty fellow of Stanford ChEM-H.
This work was funded by MCHRI, the Damon Runyon Cancer Research Study Foundation, the National Institutes of Health, the Virginia and D. K. Ludwig Fund for Cancer Research Study and Chan Zuckerberg Biohub.