Vaccine prevents pneumonia, raises high levels of protective antibodies in mice.
An experimental vaccine is effective in preventing pneumonia in mice infected with the COVID-19 virus, according to a study from the Washington University School of Medicine in St. Louis. The vaccine, which is made from a mild virus genetically modified to carry a key gene from the COVID-19 virus, is described in the journal Cell Host and Microbe.
“Unlike many of the other vaccines that have been developed, this vaccine is made from a virus that can spread in a limited way in the human body, which means it is likely to generate a strong immune response,” said co- senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser professor of medicine and a professor of molecular microbiology, and of pathology and immunology. “Since the virus is able to replicate, it can grow to high levels in the lab, so it is easy to scale up and should be more cost effective than some of the other vaccine candidates. So while what we have shown is just the proof of concept, I think it is very promising. Our vaccine candidate is now being tested in additional animal models with the aim of getting it into clinical trials as soon as possible. ”
Diamond and colleagues – including co-senior author Sean Whelan, PhD, Distinguished Professor Marvin A. Brennecke and Head of the Department of Molecular Microbiology; and co-authors Brett Case, PhD, a postdoctoral researcher in Diamond’s laboratory, and Paul W. Rothlauf, a student in Whelan’s laboratory – created the experimental vaccine by genetically modifying vesicular stomatitis virus (VSV), a livestock virus that causes but a mild disease with short life in humans. They exchanged one gene from VSV for the gene for spike of SARS-CoV-2, the virus that causes COVID-19. The hybrid virus is called VSV-SARS-CoV-2.
Spike protein is thought to be one of the keys to immunity to COVID-19. The COVID-19 virus uses spike to attach to and infect human cells, and the human body defends itself by generating protective antibodies that target spike. By adding the gene for spike to a fairly harmless virus, the researchers created a hybrid virus that, when given to humans, would ideally elicit antibodies against spike that protect against subsequent infection with the COVID-19 virus.
The same strategy was used to design the Ebola vaccine that was approved by the U.S. Food and Drug Administration in 2019. That vaccine – which is made from VSV genetically modified with a gene from the Ebola virus – is safe to thousands of people in Africa, Europe and North America, and helped end the Ebola outbreak from 2018 to 2020 in the Democratic Republic of Congo.
As part of this study, the researchers injected mice with VSV-SARS-CoV-2 as a laboratory strain of VSV for comparison. A subgroup was boosted four weeks after the initial injections with a second dose of the experimental vaccine. Three weeks after each injection, the researchers drew blood from the mice to test for antibodies that could prevent SARS-CoV-2 cells from infecting. They found high levels of such neutralizing antibodies after one dose, and the levels increased 90-fold after a second dose.
The researchers then challenged the mice five weeks after their last dose by injecting the COVID-19 virus into their noses. The vaccine completely protects against pneumonia. At four days after infection, no infected virus was detected in the lungs of mice given one or two doses of the vaccine. In contrast, mice receiving the placebo had high levels of virus in their lungs. In addition, the lungs of vaccinated mice showed fewer signs of inflammation and damage than those of mice given the placebo.
The experimental vaccine is still in the early stages of development.
Mice, of course, are not infected with the COVID-19 virus, so to assess whether the vaccine elicits a protective immune response in these, the researchers used genetically modified mice or, in unmodified mice, used a complex technique to induce susceptibility to infection. . The researchers are in the process of repeating the experiments in other animal models that are naturally susceptible to the COVID-19 virus. If the vaccine also protects those animals against COVID-19, the next step would be to scale up production under what the Food and Drug Administration refers to as “good production practice (GMP) conditions” and start a clinical trial in humans.
While the data is promising, this vaccine is still months behind in the race to develop a pandemic-ending vaccine. Six vaccines are in the final stages of testing in humans, and Anthony Fauci, MD, director of the U.S. National Institute of Allergy and Infectious Diseases, said he expects a vaccine to be ready for mass distribution early next year.
“It will really depend on how successful the first faxes that come before COVID are,” Whelan said. “If they do not produce a robust, sustained immune response when there are safety concerns, there may be a chance for a second-generation vaccine that can induce sterilizing immunity and interrupt the cycle of transmission.”
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Reference: “Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis in mice” by James Brett Case, Paul W. Rothlauf, Rita E. Chen, Natasha M. Kafai, Julie M. Fox, Brittany Smith, Swathi Shrihari, Broc T. McCune, Ian B. Harvey, Shamus P. Keeler, Louis-Marie Bloyet, Haiyan Zhao, Meisheng Ma, Lucas J.Adams, Emma S. Winkler, Michael J. Holtzman, Daved H. Fremont, Sean PJ Whelan and Michael S. Diamond, July 30, 2020, Cell Host and Microbe.
DOI: 10.1016 / j.chom.2020.07.018
Case JB, Rothlauf PW, Chen RE, Kafai NM, Fox JM, Smith B, Shrihari S, McCune BT, Harvey IB, Keeler SP, Bloyet LM, Zhao H, Ma M, Adams LJ, Winkler ES, Holtzman MJ, Fremont DH , Whelan SPJ, Diamond MS. Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis in mice. . July 30, 2020. DOI: 10.1016 / j.chom.2020.07.018
This study was supported by the National Institutes of Health (NIH), contract numbers HHSN272201700060C and 75N93019C00062 and grant numbers R01AI127828, R37AI059371, U01AI151810, R01 AI130591 and R35 HL145242; the Agency Project for Defense, grant number HR001117S0019; gifts to Washington University; and the Helen Hay Whitney Foundation.
