Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global vaccination program. The efficacy of many different versions of vaccine candidates and adjuvant effects remain unknown, particularly in the elderly. In this study, we compared the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain in young adult and aged mice, S1 with receptor binding domain, and S2 with fusion domain. Full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Old-aged mice induced SARS-CoV-2 spike-specific IgG antibodies with neutralizing activity after high dose S vaccination. With an increased vaccine dose, S1 was highly effective in inducing neutralizing and receptor-binding inhibiting antibodies, although both S1 and S2 subunit domain vaccines were similarly immunogenic. Adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses. Results of this study provide information in designing SARS-CoV-2 spike vaccine antigens and effective vaccination in the elderly.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuing to rapidly spread across the globe [1] since the first outbreak in December 2019 [2,3,4]
The full-length S coated Enzyme-Linked Immunosorbent Assay (ELISA) plates at low (0.8 μg/mL, 5.95 nM, Figure 1B) and high (2 μg/mL, 14.89 nM, Figure 1C) concentrations showed less human angiotensin-converting enzyme 2 (hACE2) binding reactivity values than those in the S1 subunit plates (10.46 and 16.1 nM, respectively). These results suggest that the S1 subunit containing receptor-binding domain (RBD) has similar or slightly higher receptor binding activity against hACE2 compared to the full-length S, possibly due to higher molarity
The old-aged mice vaccinated with a 0.8 μg dose showed more defects in inducing IgG2a than IgG1 isotype antibodies specific for full-length S compared to those of the young adult S group (Figure 2D)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuing to rapidly spread across the globe [1] since the first outbreak in December 2019 [2,3,4]. The SARS-CoV-2 S1 RBD domain binds to the host cell receptor, angiotensin-converting enzyme-2 (ACE2), and is the target for 90% of the neutralizing activity in COVID-19 convalescent sera [10]. The S glycoprotein on SARS-CoV-2 is the major target for neutralizing antibodies. Several therapeutic medications, such as neutralizing monoclonal antibodies, hydroxychloroquine, remdesivir, and dexamethasone, have been applied to treat the patients with COVID-19, but the benefits are limited or turned out to be insignificant [11,12,13,14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
