A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates

Abstract

Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take the advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLA) constructed of multivalent antigens with encapsulated TLR ligands can be used to to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based COVID-19 vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of SARS-CoV-2 S protein as the target antigen. This PLA-based vaccine candidate induced robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model we demonstrated that the viral clearance was accelerated in vaccinated animals. In addition, the PLA-based vaccine induced Th1 oriented response and a durable memory, supporting its potential for further clinic development.

Immunogenicity and protectivity of intranasally delivered vector-based heterologous prime-boost COVID-19 vaccine Sputnik V in mice and non-human primates

“…solitary neutrophils in alveolar septa) remained at 5DPI in the lungs of vaccinated animals, viral loads measured by RT–PCR (expressed viral genome copies) ( Figure 9 (A)) or by cell culture technique (TCID 50 /ml) ( Figure 9 (B)) were at undetectable levels compared to the high levels in the PBS-treated group. We believe that the observed discrepancy was caused by the nature of the immune response that needs time to utilize negative feedback loops to maintain physiological homeostasis after complete pathogen clearance rather than by the high dose of virus (that was also used for challenge study) [ 25 ].…”

Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

“…While generation of RBD-NP by fusing RBD directly to LuS resulted in poor yields, we successfully designed a two-component NP that can assemble via a SpyTag/SpyCatcher technology. As multiple two component NPs have demonstrated efficacy in preclinical and clinical studies 15 , 31 , 34 , 36 , 47 , 70 , 71 , we pursued this system that efficiently yielded pure RBD-NP. We confirmed the proper display of RBD onto NPs via ELISA employing hACE2 and anti-RBD mAbs.…”

Virus-like Particles as Antiviral Vaccine: Mechanism, Design, and Application

“…This vaccine candidate triggers neutralizing antibody production in a preclinical study, the non-adjuvanted VLPs vaccine induced a balanced Th1 and Th2 response, whereas the CPG 7909 adjuvanted formulation elicits a Th1-oriented response. In order to synergize both BCR signaling and TLR signaling, a phage (acinetobacter phage AP205) derived VLPs contains host cell derived RNA as TLRs ligands and display SARS-CoV-2 RBD on its surface is developed [112]. This VLPs construct induces a Th1-biased response and high titers of neutralizing antibodies with durable memory in NHPs.…”