A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Abstract

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response

“…These manufacturing and distribution benefits would be even more meaningful in the event that seasonal updates and mass vaccination campaigns are required. Finally, these immunogens can be easily improved by established methods of foldon trimerization, multimerization, and/or nanoparticle display 14,[32][33][34][35] .…”

SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

“…Several strategies employing similar approaches to multimerize antigens have been shown to enhance humoral immune responses to target pathogens. These include the SpyCatcher-SpyTag system, self-assembling protein nanoparticle immunogens, and several other strategies successful in generating immune responses in preclinical settings 20 – 22 . A significant advantage of employing multimeric antigen display approach is that they enrich antibody responses to specific epitopes on the target protein and induce stronger neutralizing antibody responses with lower binding antibodies targeting undesirable epitopes.…”

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

“…However, due to the presence of SARS-CoV-2, ACE2 is prevented from modulating the protein angiotensin II (ANG II), thereby causing further damage to the blood vessels of the lungs, overall preventing oxygen and carbon (IV) oxide exchange. The resultant effect is difficulty in breathing and improper functioning of the lungs, which worsen the damaging effect to the lung parenchyma, ending up in bronchitis, edema, alveolar collapse and acute respiratory distress syndrome ( Huang et al, 2020 ; Tan et al, 2021 ).…”

“…This would mean that a COVID-19 vaccine could be developed based on the spike protein sub-unit of SARS-CoV-2. In this regard, Tan and Colleagues have recently described a new vaccine candidate immunogenic against SARS-CoV-2 spike RBD, with demonstrated stability at ambient temperature; reducing cold-chain dependence ( Tan et al, 2021 ). Alternatively, the development of small molecules or antibodies that are competitive antagonists for ACE2 receptor have been explored ( Glasgow et al, 2020 ).…”

“…Alternatively, the development of small molecules or antibodies that are competitive antagonists for ACE2 receptor have been explored ( Glasgow et al, 2020 ). These agents have shown superior neutralizing efficiency to convalescent sera ( Glasgow et al, 2020 ; Tan et al, 2021 ).…”