Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development
University of Pittsburgh School of Medicine scientists announced a potential vaccine against SARS-CoV-2, the new coronavirus causing the COVID-19 pandemic. When tested in mice, the vaccine, delivered through a fingertip-sized patch, produces antibodies specific to SARS-CoV-2 at quantities thought to be sufficient for neutralizing the virus.
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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.
“We had previous experience on SARS-CoV in 2003 and MERS-CoV in 2014. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We knew exactly where to fight this new virus,” said co-senior author Andrea Gambotto, M.D., associate professor of surgery at the Pitt School of Medicine. “That’s why it’s important to fund vaccine research. You never know where the next pandemic will come from.”
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
Download the full research paper: Microneedle array delivered recombinant coronavirus vaccines
or see the press release: COVID-19 Vaccine Candidate Shows Promise
E. Kim et al., Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid
translational development, EBioMedicine (2020), https://doi.org/10.1016/j.ebiom.2020.102743
The paper appears in EBioMedicine, which is published by The Lancet