| In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China, later confirmed to be associated with infection with a new beta-coronavirus, now known as SARS-CoV-2 [118, 119]. As of 9 June 2020, over 7,131,261 cases of and 406,807 deaths due to the COVID-19 pandemic have occurred, with over 188 countries affected. Public health measures required to limit transmission have been drastic and are unlikely to be completely lifted without a vaccine (or highly efficacious prophylaxes and therapeutics). scRNA-seq can contribute to COVID-19 vaccine design, development, and evaluation. | | | Using Existing Reference Atlases | | Understanding how the virus interacts with the host has been aided by the COVID-19 Cell Atlas (http://www.covid19cellatlas.org). This collaborative has investigated the virus’s tropism by plotting the expression of genes encoding viral entry proteins in previous scRNA-seq datasets [120, 121]. SARS-CoV-2 entry genes have the highest expression in nasal goblet and airway ciliated cells [120]. Using these data to infer cell susceptibility to infection could aid in vaccine design: it would be reasonable to consider intranasal/mucosal and/or inhaled administration routes for COVID-19 vaccines. This would be in the hope of inducing local, site-specific immunity stopping the virus from entering the vasculature and organs. Indeed, Wen et al. used scRNA-seq to show that IgA, a secretory immunoglobulin, was overrepresented in early COVID-19 responses, compared to healthy controls, and may have been associated with a reduced recovery time [122]. | | | Profiling Cellular Immunity to Tailor Vaccine Responses | | A logical next step would be to generate a high-resolution multiomic cell atlas of the host immune response to COVID-19 infection in the periphery and in lung tissue [123]. Liao et al. profiled bronchoalveolar lavage immune cells in COVID-19 patients [124]. Moderate cases were characterised by the presence of highly clonally expanded CD8+ T cells with tissue-resident features. These data suggest that SARS-CoV-2-specific tissue-resident memory T cells (TRM) enable control of the virus, protecting against disease progression. Further investigation is necessary to see whether TRM-targeted vaccination is a safe and efficacious strategy against SARS-CoV-2. | | | BCR Analyses to Support mAb Development | | Using scRNA-seq to understand humoral immunity and guide vaccine-mediated antibodies against SARS-CoV-2 has shown particular promise. Wen and colleagues profiled PBMC of convalescing COVID-19 patients [122]. The BCR repertoire contained a number of highly expanded clones, notably biased usage of IGV genes and high pairing frequencies of IGHV3-23-IGHJ4 genes. Several groups have already reported the rapid identification of SARS-CoV-2-neutralising antibodies through scRNA-seq [97, 125]. Investigation of these antibodies is worthwhile as it can assist in identifying sites of vulnerability on SARS-CoV-2, antigen/epitope prioritisation and, eventually, rational design and redesign of a vaccine. | | | Research on COVID-19 is evolving quickly; many studies have not yet been peer reviewed and there have been concerns about the robustness of the peer review process of studies that have [126, 127]. Even if scRNA-seq has significant potential to aid in getting a vaccine to licensure, time will tell whether these and other studies provide proof of concept for using scRNA-seq in outbreak pathogen vaccine development. |
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