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Developmental Biology - COVID 19|
A Potential Vaccine Against SARS-CoV-2
Those animals haven’t been tracked long term yet, but researchers point out that mice who got their MERS-CoV vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far the antibody levels of the SARS-CoV-2 vaccinated animals seem to be trending the same.
Importantly, the SARS-CoV-2 microneedle vaccine maintains its potency even after being thoroughly sterilized with gamma radiation — a key step toward making a product that’s suitable for use in humans.
The authors are now in the process of applying for an investigational new drug approval from the U.S. Food and Drug Administration in anticipation of starting a phase I human clinical trial in the next few months.
When the embargo lifts, UPMC and Pitt will conduct a virtual press conference where the authors will answer questions from reporters.
Background: CCoronaviruses 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. © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license
Eun Kim, Geza Erdos, Shaohua Huang, Thomas W. Kenniston, Stephen C. Balmert, Cara Donahue Carey, V. Stalin Raj, Michael W. Epperly, William B. Klimstra, Bart L. Haagmans, Emrullah Korkmaz, Louis D. Falo Jr. and Andrea Gambotto.
AG is funded by NIH NIAID (R21-AI114264) and LDF is funded by NIH NIAMS (R01-AR074285, R01-AR071277, and R01-AR068249 to LDF). SCB is supported by a fellowship from the NIH National Cancer Institute (T32-CA175294). These funding institutions had no role in the study design, data collection, data analysis, and interpretation of this publication.
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PittCo Vacc vaccine is delivered into skin through a fingertip-sized patch of microscopic needles.
CREDIT Microneedle Array Vaccine.