125 Nanoparticles presenting a high density of antigen on a repetitive array facilitate numerous 126 immunological processes such as B cell activation, lymph node trafficking and retention on 127 follicular dendritic cells (Kelly et al., 2019 Tokatlian et al., 2019). 122 123 A well established st rategy to generate strong humoral immune responses against soluble 124 antigens is m ultivalent antigen display (Bachmann and Jennings, 2010 Moyer et al., 2016). In addition, recombinantly expressed S proteins represent an 120 efficient antigen to induce potent NAb responses, as recently reported in non-human primate 121 studies (Guebre-Xabier et al., 2020 Liang et al., 2020 Tian et al., 2020). 117 Recombinant subunit vaccines provide a welcome alternative to the inactivated, viral vector 118 and RNA-based vaccines that are currently in Phase III clinical trials, as they have a track 119 record of safety and eff icacy. 114ฤก15 More than 200 candidate vaccines are currently under preclinical or clinical evaluation 116 ( dscape-of-covid-19-candidate-vaccines). As most NAb epitopes are presented on the 110 prefusion conformation, vaccine candidates should include the prefusion S protein, which as 111 for other class I viral fusion proteins (Krarup et al., 2015 Sanders et al., 2002), can be 112 stabilized by appropriately positioned proline substitutions (Pallesen et al., 2017 Walls et al., 113 2020a Wrapp et al., 2020). Upon binding to ACE2, the prefusion S protein undergoes several structural 108 changes that induce a shift to a postfusion state that enables merging of the viral envelope 109 and host cell membrane (Shang et al., 2020). This homotrimeric glycoprotei n is anchored in the viral membrane and 105 consists of the S1 domain, containing the receptor-binding domain (RBD) for the host cell 106 receptor angiotensin converting enzyme-2 (ACE2), and the S2 domain, which contains the 107 fusion peptide. The main target for NAbs on SARS-CoV-2 is t he 104 spike (S) protein. T hus, a successful vaccine will likely 103 need to induce a potent NAb response. This is 100 supported by several passive immunization studies showing that administration of potent 101 neutralizing SARS-CoV-2-specific monoclonal antibodies (mAbs) can significantly reduce 102 lung viral loads ( Cao et al., 2020 Rogers et al., 2020).
98 Recent studies suggest t hat SARS-CoV-2-specific neutralizing antibody (NAb) titers are an 99 important immune correlate of protection (Adde tia et al., 2020 Yu et al., 2020 ).