Getting Ahead of COVID-19 Variants

Viruses are constantly changing through mutation, and currently, there are several variants of the SARS-CoV-2 virus that causes COVID-19. Considering these emerging variants, BioCentury described how vaccine and antibody developers are adapting their strategy.

Researchers in the early stages of developing therapies need to focus on creating resilient treatments to as many variants as possible. At the same time, many developers of first-generation COVID vaccines and antibodies are working on new medicines to address variants of SARS-CoV-2. Switching to new candidates comes at an immense cost in time, R&D investments, and supply. For example, Carl Hansen, the CEO of AbCellera, said switching gears to a new candidate would require them to sacrifice some supply of the previous antibody.

Researchers and pharmaceutical companies can study countermeasures in animal models to evaluate their efficacy against variants of SARS-CoV-2 in a highly controlled experimental environment at a reduced cost. Preclinical studies also permit detailed immunological profiling that is not possible in clinical trials. This is shown by Dr. Diamond et al. recent publication where his lab measured impaired flexiVent lung function in k18-hACE2 mouse models of COVID-19 at day seven post-infection. Additional studies by this lab demonstrate prophylactic treatment of LCB1, an ultrapotent miniprotein, prevents SARS-CoV-2-mediated flexiVent lung function decline in preclinical disease modelling.

Furthermore, numerous studies based on hamster and k18-hACE2 mouse models have provided insights into vaccination and therapeutic strategies with monoclonal antibodies (mABs) in humans exposed to SARS-CoV-2. For example, studies carried out at UTMB showed that administration of Moderna’s mRNA-1273 vaccine in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease (Meyer et al., 2021).

In vivo experiments in k18-hACE2 mice and hamsters can provide novel insights into viral escape routes from authorized vaccines and therapies and guide governments and drug design companies towards the most productive strategies. Johnson et al (2020) showed that mutant SARS-CoV-2 virus lacking the spike furin cleavage site led to attenuated SARS-CoV-2 pathogenesis in k18-hACE2 mice and hamsters using clinically-relevant flexiVent lung function outcomes.

With predictive preclinical in vivo lung function assays, drug and vaccine developers can assess how their molecules will perform against emerging variants of SARS-CoV-2 and adapt their development strategies. Researchers and pharmaceutical companies should test next-generation vaccine or therapy strategies in predictive preclinical models to offer the earliest and best protection possible against variants.

Wondering which preclinical model to choose for your COVID Research? Find out what the experts have to say.

Watch the recording of the Preclinical Models of COVID-19 Panel Discussion

References

Case, J. B., Chen, R. E., Cao, L., Ying, B., Winkler, E. S., Johnson, M., … & Diamond, M. S. Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease. Cell Host & Microbe.

Meyer, M., Wang, Y., Edwards, D., Smith, G. R., Rubenstein, A. B., Ramanathan, P., … & Bukreyev, A. (2021). mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge. bioRxiv.

Johnson, B. A., Xie, X., Bailey, A. L., Kalveram, B., Lokugamage, K. G., Muruato, A., … & Menachery, V. D. (2021). Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature591(7849), 293-299.

Sandi Wong, A. E. (2021, February 12). How COVID-19 drug developers can stay ahead of viral variants. Retrieved June 21, 2021, from https://www.biocentury.com/article/633954/how-covid-19-drug-developers-can-stay-ahead-of-viral-variants

Stevens, C. (2020, April 11). The Origins of SARS-CoV-2: Part 2. Retrieved July 21, 2021, from https://leelabvirus.host/covid19/origins-part2

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