Abstract
SummaryThe SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.
Highlights
A severe acute respiratory disease syndrome caused by a novel coronavirus was first reported in December 2019 (COVID-19 disease) and was subsequently shown to be caused by SARS-CoV2 (Zhou et al, 2020)
Production, and stability of AAVCOVID vaccines AC1 and AC3 are viral vector COVID-19 vaccine candidates composed of an AAVrh32.33 capsid and an AAV2 inverted terminal repeat (ITR)-flanked transgene-expressing distinct SARSCoV-2 S antigens (Figure 1A)
AC1 encodes a full-length membrane anchored S protein (Wuhan strain) mutated to abrogate the S1/S2 furin cleavage site and to lock its pre-fusion conformation to allow for optimal receptor-binding domain (RBD) antigenicity (Walls et al, 2020; Wrapp et al, 2020)
Summary
A severe acute respiratory disease syndrome caused by a novel coronavirus was first reported in December 2019 (COVID-19 disease) and was subsequently shown to be caused by SARS-CoV2 (Zhou et al, 2020). Based on prior work on SARS-CoV-1 and other respiratory viruses, the SARS-CoV-2 spike protein (S) was considered an attractive antigen target for the induction of protective immunity to the virus (Folegatti et al, 2020a; Graham et al, 2020; Koch et al, 2020; Martin et al, 2008; Modjarrad et al, 2019; Muthumani et al, 2015; van Doremalen et al, 2020a). The utility of employing this antigen as a vaccination target has been validated by reports of substantial protective efficacy in several human vaccine studies (Folegatti et al, 2020b; Jackson et al, 2020)
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