Objectives Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion‐stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 ‘MF59C.1’ (Seqirus, Parkville, Australia). Methods A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo‐electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. Results In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S‐specific CD4 + and cytotoxic CD8 + T cells in vivo . In the Syrian hamster challenge model ( n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. Conclusion The SARS‐CoV‐2 Sclamp vaccine candidate is compatible with large‐scale commercial manufacture, stable at 2–8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T‐cell responses and provides protection in animal challenge models.

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Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution.

Despite over 60 years' worth of taxonomic efforts, the relationships between sugarcane (Saccharum hybrid cultivars), Sorghum and their closest evolutionary relatives remain largely unresolved. Even relationships between generally accepted genera such as Miscanthus and Saccharum have not been examined in any large-scale molecular detail. Genera such as Erianthus, Miscanthidium and Narenga pose even greater taxonomic contention. Erianthus is not monophyletic and Erianthus sect. Ripidium (Valdés and Scholz 2006, Lloyd Evans et al. 2019a; Welker et al. 2019) represents a distinct and separate genus, Tripidium Scholz. Miscanthidium is placed within Miscanthus by many workers, whilst the New World Erianthus species and Narenga are currently placed within Saccharum. As these species represent a significant portion of the gene pool that sugarcane breeders use for introgression into sugarcane, their taxonomic placement and relationships to Saccharum are of significant economic import. Erianthus species from the Americas have not been significantly employed in sugarcane breeding and may represent an untapped genetic resource. In an attempt to resolve the taxonomic relationships of these genera, we have assembled three novel chloroplasts, from Miscanthidium capense, Miscanthidium junceum and Narenga porphyrocoma (this latter assembled from transcriptomic and long read data). In parallel, five low copy number loci have been assembled from species within Saccharum, Miscanthus, Sarga and Sorghum. Phylogenetic analyses were performed using both low copy number genes and whole chloroplasts. The phylogenetic results were compared with karyotype data to circumscribe the genera most closely related to sugarcane. We reveal that genera Miscanthus and Saccharum are monophyletic and have never undergone polyploidization outside their own genera. Genera Erianthus, Miscanthidium and Narenga are allopolyploids, which excludes them from being members of Saccharum and Miscanthus. Moreover, all three of these genera have divergent evolutionary histories. We therefore support the use of the genera Miscanthus, Miscanthidium, Erianthus (for the New World Species) and Narenga for those species and genera most closely allied to Saccharum. Our data demonstrate that all these genera should be excluded from Saccharum sensu lato.