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Recombinant Coronavirus Vaccines Delivered via Microneedle Array

Curator: Irina Robu, PhD

Coronavirus is an evolving pathogen with exponentially increasing significance due to the high case fatality rate, the large distribution of reservoir, and the lack of medical countermeasures. The public health emergencies triggered by coronaviruses, including SARS-CoV and SARS-CoV-2, obviously validate the urgency to assess candidate vaccines to fight these outbreaks. Continuous research contributes to the efforts of scientists to quickly progress safe vaccines against these developing infections. The recent COVID-19 pandemic indicates a vital need for the rapid design, production, testing, and clinical translation of candidate vaccines.

Coronavirus virus particles contain four main structural proteins. These are the spike, membrane, envelope, and nucleocapsid proteins, all of which are encoded within the 3′ end of the viral genome. Coronaviruses contain a non-segmented, positive-sense RNA genome, which contains a 5′ cap structure along with a 3′ poly (A) tail, allowing it to act as a mRNA for translation of the replicase polyproteins. The replicase gene encoding the nonstructural proteins inhabits two-thirds of the genome, which make up only about 10 kb of the viral genome. The 5′ end of the genome contains a leader sequence and untranslated region that encompasses multiple stem loop structures required for RNA replication and transcription. Furthermore, at the start of each structural gene are the transcriptional regulatory sequences that are essential for expression of each of these genes.

Researchers at U of Pittsburg generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. They engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists) into this trimeric design and tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice, distributed subcutaneously by needle injection or intracutaneously by dissolving microneedle arrays by assessing virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays.

Microneedle array mediated immunization has several mechanistic differences from traditional intramuscular needle injections, which could clarify the variations in the magnitude and kinetics of the ensuing responses. Due to the urgent need for COVID-19 vaccines, they used this approach to quickly advance MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in-vivo by manipulating the previous research on MNA MERS-CoV vaccines.

Even though it is still premature to predict whether humans immunized with these vaccine candidates will have similar responses and be protected from SARS-CoV-2 infections, their previous research show that development, production, and initial animal testing of clinically translatable MNA vaccine candidates against SARS-CoV-2. Incidentally it will be vital to determine whether antibodies from MNA-SARS-CoV-2 immunized animals will neutralize virus infectivity.

Finally, we note that the immunogenicity differences between MNA coronavirus vaccines and coronavirus vaccines delivered by traditional needle injection that we observe will need to be evaluated in clinical trials to establish the clinical advantages of MNA delivery.

SOURCE

E. Kim et al., Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development, EBioMedicine (2020).

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