Project description:The SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.

| S-EPMC9979983 | biostudies-literature

Development of an RBD-Fc fusion vaccine for COVID-19.

Project description:Although the global pandemic of SARS-CoV-2 has passed, there are still regional outbreaks that continue to jeopardize human health. Hence, there is still a great deal of interest in developing an efficient vaccine that can quickly and effectively prevent reemerging outbreaks of SARS-CoV-2. Delta variant was once a dominant strain in the world in 2021, and we first constructed a recombinant RBDdelta-Fc fusion vaccine by coupling the RBD of Delta variant with the human Fc fragment. This Fc fusion strategy increases the immunogenicity of the recombinant RBD vaccine, with a long-lasting high level of IgG antibodies and neutralizing antibodies induced by RBDdelta-Fc vaccine. This RBDdelta-Fc vaccine, as well as the RBD-Fc vaccine prepared in our previously study, could trigger a durable immune effect by the heterologous boosting immunity, and the RBD-Fc induced a quicker humoral immune response than the homologous immunization with inactivated vaccines. In conclusion, the Fc fusion strategy has a significant role in enhancing the immunogenicity of recombinant protein vaccines, thus promising the development of a safe and efficient vaccine for the heterologous boosting against SARS-CoV-2.

| S-EPMC10847155 | biostudies-literature

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine as a heterologous booster.

Project description:To overcome the increased risk of SARS-CoV-2 reinfection or post-vaccination infection caused by the Omicron variant, Omicron-specific vaccines were considered a potential strategy. We reported the increased magnitude and breadth of antibody response against VOCs elicited by post-vaccination Delta and Omicron infection, compared to WT infection without vaccination. Then, in mouse models, three doses of Omicron-RBD immunization elicited comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, a heterologous Omicron-RBD booster following two doses of WT-RBD immunization increased the NAb titers against Omicron by 9-folds than the homologous WT-RBD booster. Moreover, it retains neutralization against both WT and current VOCs. Results suggest that Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs and that SARS-CoV-2 vaccines including two or more virus lineages might improve the NAb response.

| S-EPMC9621588 | biostudies-literature

Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine.

Project description:With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine (IV) in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

| S-EPMC9979697 | biostudies-literature

Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants.

Project description:We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants.

| S-EPMC10403593 | biostudies-literature

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants.

Project description:Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

| S-EPMC9481243 | biostudies-literature

Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine.

Project description:AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60-68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

| S-EPMC10881471 | biostudies-literature

SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster.

Project description:The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we measured neutralizing antibodies against Omicron in three important settings: (1) post-vaccination sera after two and three immunizations with the Pfizer/BNT162b2 vaccine, (2) convalescent sera from unvaccinated individuals infected by different variants, and (3) clinical-stage therapeutic antibodies. Using a pseudovirus neutralization assay, we found that titers against Omicron were low or undetectable after two immunizations and in most convalescent sera. A booster vaccination significantly increased titers against Omicron to levels comparable to those seen against the ancestral (D614G) variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. Only three of 24 therapeutic antibodies tested retained their full potency against Omicron and high-level resistance was seen against fifteen. These findings underscore the potential benefit of booster mRNA vaccines for protection against Omicron and the need for additional therapeutic antibodies that are more robust to highly mutated variants.One sentence summaryThird dose of Pfizer/BioNTech COVID-19 vaccine significantly boosts neutralizing antibodies to the Omicron variant compared to a second dose, while neutralization of Omicron by convalescent sera, two-dose vaccine-elicited sera, or therapeutic antibodies is variable and often low.

| S-EPMC8722594 | biostudies-literature

Neutralization of Omicron XBB.1 by booster vaccination with BA.4/5 monovalent mRNA vaccine.

Project description: Not available

| S-EPMC10774259 | biostudies-literature