Using new technology, scientists in Pittsburgh have unveiled in record time what they believe is a Covid-fighting vaccine. Importantly, if the vaccine is effective, it can be mass produced and rapidly unleashed against the pandemic, the scientists said.
The researchers at the University of Pittsburgh School of Medicine today said they think their vaccine can be distributed fast enough to “significantly impact the spread of disease,” according to their study in EBioMedicine, which is published by The Lancet. Because of the emergency situation, the Pittsburgh scientists were hoping to drastically speed up the usual time period of a year or so for human clinical trials. The federal Food and Drug Administration must approve any human testing of the vaccine candidate.
The researchers also used a novel approach for delivering the drug via a "microneedle array," as a means of increasing potency. This array is a fingertip-sized patch of 400 tiny needles that "delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles -- which are made entirely of sugar and the protein pieces -- simply dissolve into the skin," according to a university statement.
"We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient," according to Louis Falo, M.D., Ph.D., professor and chair of dermatology at Pitt's School of Medicine. "And it's actually pretty painless -- it feels kind of like Velcro."
The scientists' experience with the coronaviruses known as Sars and Mers, which are closely related to the Covid virus, gave them a leg up in their research, a university statement said.
“These two viruses, which are closely related to Sars-Cov-2" -- which is the name of the virus that triggers the disease Covid-19 -- "teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus,” according to a statement from Andrea Gambotto, M.D., associate professor of surgery at the Pitt School of Medicine and a study author. “We knew exactly where to fight this new virus.”
The vaccine follows the traditional approach of ordinary flu vaccines, using lab-made pieces of viral protein to build immunity.
While the mice have not been studied over a long period of time, the vaccine was able to deliver hard-hitting antibodies against the Covid virus within two weeks, according to the researchers. Those animals have not yet been tracked long-term but the researchers point out that previously mice that received Mers-Cov vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year. So far, the scientists said, the same trend has appeared in the antibody levels of the animals vaccinated against Covid.
Scientists in a statement said the "system also is highly scalable," adding, "The protein pieces are manufactured by a 'cell factory' -- layers upon layers of cultured cells engineered to express" the Covid virus's spike protein. "Purifying the protein also can be done at an industrial scale" and the micro-needle patch can be mass produced. Further, the vaccine can be stored at room temperature, university officials said.
"For most vaccines, you don't need to address scalability to begin with," Gambotto said. "But when you try to develop a vaccine quickly against a pandemic, that's the first requirement."
Additional authors on the study are Eun Kim, Geza Erdos, Ph.D., Shaohua Huang, Thomas Kenniston, Stephen Balmert, Ph.D., Cara Donahue Carey, Michael Epperly, Ph.D., William Klimstra, Ph.D., and Emrullah Korkmaz, Ph.D., all of Pitt; and Bart Haagmans, of Erasmus Medical Center.
Abstract of the vaccine paper in EBiomedicine
Background
Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection.
Methods
We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines.
Findings
Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization.
Interpretation
MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.
The researchers at the University of Pittsburgh School of Medicine today said they think their vaccine can be distributed fast enough to “significantly impact the spread of disease,” according to their study in EBioMedicine, which is published by The Lancet. Because of the emergency situation, the Pittsburgh scientists were hoping to drastically speed up the usual time period of a year or so for human clinical trials. The federal Food and Drug Administration must approve any human testing of the vaccine candidate.
The researchers also used a novel approach for delivering the drug via a "microneedle array," as a means of increasing potency. This array is a fingertip-sized patch of 400 tiny needles that "delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles -- which are made entirely of sugar and the protein pieces -- simply dissolve into the skin," according to a university statement.
"We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient," according to Louis Falo, M.D., Ph.D., professor and chair of dermatology at Pitt's School of Medicine. "And it's actually pretty painless -- it feels kind of like Velcro."
The scientists' experience with the coronaviruses known as Sars and Mers, which are closely related to the Covid virus, gave them a leg up in their research, a university statement said.
“These two viruses, which are closely related to Sars-Cov-2" -- which is the name of the virus that triggers the disease Covid-19 -- "teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus,” according to a statement from Andrea Gambotto, M.D., associate professor of surgery at the Pitt School of Medicine and a study author. “We knew exactly where to fight this new virus.”
The vaccine follows the traditional approach of ordinary flu vaccines, using lab-made pieces of viral protein to build immunity.
While the mice have not been studied over a long period of time, the vaccine was able to deliver hard-hitting antibodies against the Covid virus within two weeks, according to the researchers. Those animals have not yet been tracked long-term but the researchers point out that previously mice that received Mers-Cov vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year. So far, the scientists said, the same trend has appeared in the antibody levels of the animals vaccinated against Covid.
Scientists in a statement said the "system also is highly scalable," adding, "The protein pieces are manufactured by a 'cell factory' -- layers upon layers of cultured cells engineered to express" the Covid virus's spike protein. "Purifying the protein also can be done at an industrial scale" and the micro-needle patch can be mass produced. Further, the vaccine can be stored at room temperature, university officials said.
"For most vaccines, you don't need to address scalability to begin with," Gambotto said. "But when you try to develop a vaccine quickly against a pandemic, that's the first requirement."
Additional authors on the study are Eun Kim, Geza Erdos, Ph.D., Shaohua Huang, Thomas Kenniston, Stephen Balmert, Ph.D., Cara Donahue Carey, Michael Epperly, Ph.D., William Klimstra, Ph.D., and Emrullah Korkmaz, Ph.D., all of Pitt; and Bart Haagmans, of Erasmus Medical Center.
Abstract of the vaccine paper in EBiomedicine
Background
Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection.
Methods
We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines.
Findings
Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization.
Interpretation
MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.
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