Rapid Development of Analytical Methods for Evaluating Pandemic Vaccines: A Covid-19 Perspective

Abstract

Vaccines are key in charting a path out of the COVID-19 pandemic. However, development of new vaccines is highly dependent on availability of analytical methods for their design and evaluation. This paper highlights the challenges presented in having to rapidly develop vaccine analytical tools during an ongoing pandemic, including the need to address progressive virus mutation and adaptation which can render initial assays unreliable or redundant. It also discusses the potential of new computational modeling techniques to model and analyze key viral proteins and their attributes to assist vaccine production and assay design. It then reviews the current range of analytical tools available for COVID-19 vaccine application, ranging from in vitro assays for immunogen characterization to assays to measure vaccine responses in vivo. Finally, it provides a future perspective for COVID-19 vaccine analytical tools and attempts to predict how the field might evolve over the next 5–10 years.

Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters

“…The termination at day 3 post-challenge was based on findings in previous studies that even unimmunized hamsters show peak SARS-CoV-2 viral titers by day 2 with subsequent rapid clearance by day 4, making later time points not useful for assessing vaccine effects [40] . Another limitation was that similar to other COVID-19 hamster studies [41] , [42] , [43] , [44] , our hamsters were challenged just 2 weeks after the final immunization [45] . Emerging data suggests that immunity induced by adenoviral and mRNA vaccines might rapidly wane over months, leading to loss of protection [46] .…”

Evaluating the efficacy and safety of SpikoGen®, an Advax-CpG55.2–adjuvanted severe acute respiratory syndrome coronavirus 2 spike protein vaccine: a phase 3 randomized placebo-controlled trial

“…Algorithms have been developed based on extrapolations from antibody levels and virus neutralization assays to predict overall vaccine efficacy against ancestral strains [12,13]. We therefore evaluated our previously published Phase 2 trial data [7] to determine what might have been the likely efficacy of SpikoGen® against the ancestral strains.…”

Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations

“…32 While sequencing provides high information content, the upfront mRNA enrichment, isolation, amplification, ligation, and other sample processing and data analysis steps significantly increase complexity, time to result, and cost which may limit adoption by lower-and middle-income country vaccine manufacturers. 33 While more straightforward than sequencing, RT-PCR based identity testing still requires special workflows and sample handling to eliminate potential for cross-contamination with amplifiable nucleic acids and requires upfront purification if the mRNA is encapsulated in a lipid nanoparticle (LNP). 32,33 Recommended methods for mRNA quantitation are PCR-based methods and UV spectroscopy.…”

“…33 While more straightforward than sequencing, RT-PCR based identity testing still requires special workflows and sample handling to eliminate potential for cross-contamination with amplifiable nucleic acids and requires upfront purification if the mRNA is encapsulated in a lipid nanoparticle (LNP). 32,33 Recommended methods for mRNA quantitation are PCR-based methods and UV spectroscopy.…”

“…These current methodologies were adopted out of the urgent need for COVID-19 vaccines to address the pandemic, and the speed of development was laudable. 11,17,20,33 While future mRNA vaccines may not be developed at quite the same pace as those for COVID-19, anticipated accelerated development timelines compared to traditional vaccines and an increase in development of multivalent mRNA vaccines highlight the need for improved, rapid analytical tools that can streamline bioprocess development and optimization, formulation development, and QC testing to further reduce time to market and improve between-lab standardization. 21,32,34 In this work, we demonstrate performance of a model multiplexed nucleic acid microarray-based assay for influenza mRNA vaccine construct identity and quantification.…”