A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge

Abstract

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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

“…Herein, we describe the results of a statistically-balanced nonhuman primate study in which we evaluated the efficacy of SARS-CoV-2 SpFN protein nanoparticle vaccine against a robust and high-titer SARS-CoV-2 respiratory (IT) and mucosal (IN) challenge. Efficacy and/or immunogenicity of this vaccine has been demonstrated in mice, hamsters, and rhesus macaques [17, 19, 31], including efficacy against the Alpha and Beta variants of SARS-CoV-2 demonstrated in hamsters [19]. CM were chosen for the present study as this model reproduces several human disease characteristics and provides two ideal objective and relevant endpoint criteria for efficacy evaluations: fever and viral RNA in nasopharyngeal swabs [20, 21].…”

“…We previously reported the immunogenicity of SpFN adjuvanted with either aluminum hydroxide (AlOH3) or Army Liposomal Formulation QS-21 (ALFQ) in mice, and observed increased humoral and T cell responses with ALFQ [17]. Subsequent vaccine efficacy studies of SpFN-ALFQ demonstrated protection against disease and viral replication in the respiratory tract of Syrian golden hamsters, and against viral replication in rhesus macaques [18, 19].…”

Mosaic receptor-binding domain nanoparticles induce protective immunity against SARS-CoV-2 challenges

“…RBD monomer, dimer and trimer antigens elicited potent Ab responses 9, 10, 13 , while highly ordered and repetitive structures of RBDs mimicked the organization and density of antigens on natural virions, to be of great advantage in promoting protective immunity 17, 46, 47 . Self-assembling multivalent RBD or spike nanoparticles using SpyTag/SpyCatcher or sortase-mediated ligation and computationally designed scaffolds, ferritin, or lumazine synthase fusion platforms have shown high potentiation of immune responses against COVID-19 17–19, 47, 48 . However, administration of homotypic multivalent antigens or possibly multiple booster doses with strain-specific antigens can lead to over-specialization of the B cells with limited breadth of antigen recognition 26 .…”

“…Nevertheless, nAbs against multiple variants are currently accepted as a correlate of protection 12, 37 , and the RBD indeed accounts for more than 90% of the neutralizing activity in sera from COVID-19 convalescent and vaccinated individuals 9–12 . RBD monomer, dimer and trimer antigens elicited potent Ab responses 9, 10, 13 , while highly ordered and repetitive structures of RBDs mimicked the organization and density of antigens on natural virions, to be of great advantage in promoting protective immunity 17, 46, 47 . Self-assembling multivalent RBD or spike nanoparticles using SpyTag/SpyCatcher or sortase-mediated ligation and computationally designed scaffolds, ferritin, or lumazine synthase fusion platforms have shown high potentiation of immune responses against COVID-19 17–19, 47, 48 .…”

Nasal Nanovaccines for SARS-CoV-2 to Address COVID-19

“…The development of candidate vaccines based on protein assemblies is a powerful strategy. Ferritin self-assembled NPs are already in clinical trials as nasal nanovaccines [ 68 ] ( Table 1 ).…”