Single-dose respiratory mucosal delivery of next-generation viral-vectored COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2 (preprint)

The emerging SARS-CoV-2 variants of concern (VOC) increasingly threaten the effectiveness of current first-generation COVID-19 vaccines that are administered intramuscularly and are designed to only target the spike protein. There is thus a pressing need to develop next-generation vaccine strategies to provide more broad and long-lasting protection. By using adenoviral vectors (Ad) of human and chimpanzee origin, we developed Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens and evaluated them following single-dose intramuscular or intranasal immunization in murine models. We show that respiratory mucosal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the three-arm immunity, consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity. We further show that single-dose intranasal immunization provides robust protection against not only the ancestral strain of SARS-CoV-2, but also two emerging VOC, B.1.1.7 and B.1.351. Our findings indicate that single-dose respiratory mucosal delivery of an Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy against current and future VOC. This strategy has great potential to be used not only to boost first-generation vaccine-induced immunity but also to expand the breadth of protective T cell immunity at the respiratory mucosa.

Probe Design for Simultaneous, Targeted Capture of Diverse Metagenomic Targets (preprint)

The compounding challenges of low signal, high background, and uncertain targets plague many sequencing efforts, including monitoring potential zoonotic resevoirs. One solution has been targeted DNA capture, where probes are designed to hybridize with target sequences, enriching them relative to the background. We have developed the HUBDesign pipeline which makes use of sequence homology to design probes at multiple taxonomic levels. This creates an efficient probe set capable of simultaneously and specifically capturing known and potentially novel sequences. We validated HUBDesign by generating a probe set targeting the breadth of coronavirus diversity. We demonstrated significant enrichment of SARS-CoV-2 and HCoV-NL63 from a human background, without interference between the two viruses, nor background enrichment. This probe set will be of use in identifying coronavirus co-infections and surveillance of coronaviruses resevoirs. HUBDesign has broad applicability wherever there are multiple organisms of interest, such as ancient DNA, and host specific microbiomes.Funding Statement: This work was partially supported by CIHR COVID-19 Rapid Response funding to MSM. MSM was supported in part by a CIHR New Investigator Award and an Early Career Researcher Award from the Government of Ontario. This work was partially funded by a CIHR COVID grant to Principal applicant KM and co-applicant AB. AB, HP, GBG, and ZWD were funded through Natural Sciences and Engineering Research Council of Canada.HP was generously funded by the Boris Family Fund, the Micheal G. DeGroote Institute for Infectious Disease Research.Declaration of Interests: None to declareEthics Approval Statement: Work with SARS-CoV-2 was performed in a containment level 3 laboratory and all protocols were approved by the McMaster Presidential Biosafety Advisory Committee.