The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines.

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus–host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.

Plant-associated microbes are critical players in host health, fitness and productivity. Despite microbes’ importance in plants, seeds are mostly sterile, and most plant microbes are recruited from an environmental pool. Surprisingly little is known about the processes that govern how environmental microbes assemble on plants in nature. In this study we examine how bacteria are distributed across plant parts, and how these distributions interact with spatial gradients. We sequenced amplicons of bacteria from the surfaces of six plant parts and adjacent soil of Scaevola taccada, a common beach shrub, along a 60 km transect spanning O’ahu island’s windward coast, as well as within a single intensively-sampled site. Bacteria are more strongly partitioned by plant part as compared with location. Within S. taccada plants, microbial communities are highly nested: soil and rhizosphere communities contain much of the diversity found elsewhere, whereas reproductive parts fall at the bottom of the nestedness hierarchy. Nestedness patterns suggest either that microbes follow a source/sink gradient from the ground up, or else that assembly processes correlate with other traits, such as tissue persistence, that are vertically stratified. Our work shines light on the origins and determinants of plant-associated microbes across plant and landscape scales.