Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice

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.

Plant-Produced S1 Subunit Protein of SARS-CoV-2 Elicits Immunogenic Responses in Mice

“…Previous report showed that the SARS-CoV-2 S1 subunit protein can stimulate the SARS-CoV-2 S1-specific IgG titer higher than the SARS-CoV-2 RBD protein when using the SARS-CoV-2 S1 protein and SARS-CoV-2 RBD protein as a coating antigen in ELISA [28]. Further, alum adjuvant can enhance the Th-2 (IgG1) immune response better than the Th-1 (IgG2a) immune response [45], which confirmed in the present study that the SARS-CoV-2 RBD-specific IgG1 antibody responses were increased more than the SARS-CoV-2 RBD-specific IgG2a antibody responses [27,45].…”

“…Moreover, the receptor binding domain (RBD) from the S1 subunit induced significant immune response and neutralizing antibodies which were evident from several studies [14,15]. The full length of the S1 subunit also can stimulate the immune response and the neutralization antibodies to block the viral infection [27][28][29]. As a result, the S1 subunit in the S protein could be a target for developing an effective SARS-CoV-2 vaccine.…”

Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice

“…In the context of SARS-CoV-2 vaccines there have been numerous adjuvants that have shown beneficial effects on immunogenicity [46][47][48][49] . Interestingly, a AS01-like adjuvanted SARS-CoV-2 subunit vaccine enhanced Th1-type IgG2a isotype and IFN-γ secreting T cell immune responses in BALB/c mice when compared to unadjuvanted control 61 .…”

SARS-CoV-2 S1 Subunit Booster Vaccination Elicits Robust Humoral Immune Responses in Aged Mice

“…Actually, AS03-adjuvanted CoV2 preS dTM (B.1.351) induced higher neutralizing antibody titers against Beta variant in non-human primates compared to animal group boosted with non-adjuvanted vaccine in the mRNA-primed cohort [21]. AS01-like adjuvanted SARS-CoV-2 subunit vaccine enhanced Th1 type-IgG2a isotype, neutralizing antibodies, and IFN-γ secreting T cell immune responses in both young and aged mice [45]. Recombinant S protein in combination with adjuvant CoVaccine HT™ induced a balanced IgG subtype antibody response [41].…”