Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Abstract

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

Scientific rationale for developing potent RBD-based vaccines targeting COVID-19

“…Preclinical studies have evaluated the protective efficacy of several RBD-specific monoclonals, as well as RBD as a protective immunogen. Investigators evaluating RBD as a vaccine candidate have delivered the antigen either as DNA 81 , mRNA 7,74,[82][83][84][85] , viral vector 86 , soluble monomer or dimer 6,22,[87][88][89][90][91][92][93] , a fusion protein nanoparticle 16,26,[94][95][96][97][98] , or as a virus-like particle (VLP) 91,[99][100][101][102] . Additional RBD-based vaccine candidates in clinical trials (Table 2)…”

“…Vaccine researchers around the world have demonstrated preclinical immunogenicity of multimeric RBD vaccine candidates utilizing a variety of presentation methods including the following: ferritin nanoparticles 94,96,98,108,109 , single-component protein nanoparticles 95 , two-component protein nanoparticles either self-assembling 26 or assembled via SpyTag/Catcher technology 91,99,110 , and VLPs 102,111 . Together, these studies support the assertion that RBD displayed on a particle and co-administered with a suitable adjuvant represents a viable vaccine strategy for SARS-CoV-2, including against VOC.…”

A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model

“…The SARS-CoV-2 SpFN nanoparticle vaccine contains the SARS-CoV-2 spike (S) glycoprotein (truncated at residue 158) linked to the H. pylori ferritin nanoparticle. Transfection, expression, and purification of SpFN was carried out as previously described [33][34][35]. In brief, an expression plasmid was transiently transfected into Expi293F cells using ExpiFectamine 293 transfection reagent and culture supernatants were harvested 4-5 days after transfection, filtered with a 0.22-µm filter.…”

A mRNA vaccine encoding for a RBD 60-mer nanoparticle elicits neutralizing antibodies and protective immunity against the SARS-CoV-2 delta variant in transgenic K18-hACE2 mice

“…Structure-based antigen design is a widely used approach to improve immunogenicity (Graham et al, 2019; Irvine and Read, 2020; Singh, 2021) and has been applied to the RBD either by creating RBD multimers or displaying the RBD onto protein or synthetic nanoparticles (NPs) (Borriello et al 2021, Cohen et al, 2021; Dalvie et al, 2021; He et al, 2021; King et al, 2021; Ma et al, 2020; Peachman et al, 2021; Tan et al, 2021; Walls et al, 2020b; Walsh et al, 2020). The main objective of these various designs is to increase antigen trafficking into draining lymph nodes and to promote B cell receptor clustering and B cell activation.…”