Project description:Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

| S-EPMC9906998 | biostudies-literature

Bivalent COVID-19 mRNA vaccine against omicron subvariants in immunocompromised patients.

Project description: Not available

| S-EPMC10281643 | biostudies-literature

Monovalent Omicron COVID-19 vaccine triggers superior neutralizing antibody responses against Omicron subvariants than Delta and Omicron bivalent vaccine.

Project description:The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses a challenge to determine the optimal updated composition of the coronavirus disease 2019 (COVID-19) vaccine. The present study aimed to investigate the immunogenicity of the Delta monovalent vaccine, the Omicron monovalent vaccine, and the Delta and Omicron BA.1 bivalent vaccine. Three COVID-19 vaccines were designed using the heterologous DNA prime-protein boost strategy, with each vaccine containing either Delta receptor-binding domain (RBD) of the spike protein, Omicron RBD, or both Delta and Omicron antigens. Temporal serum antibody binding titers and neutralizing antibody titers induced by the three vaccines in New Zealand White rabbits were analyzed. To further dissect the vaccine elicited antibodies (mAb) responses at the molecular level, a panel of rabbit monoclonal antibodies (RmAbs) was generated by a high-throughput single B cell sorting and discovery pipeline and further comprehensively characterized. The Omicron monovalent vaccine induced higher antibody binding titers and neutralization activities than the Delta and Omicron bivalent vaccine. Four RmAbs with robust neutralization capacity were isolated from rabbits immunized with the Omicron or Delta monovalent vaccine. Notably, 9E11 isolated from the Omicron monovalent vaccine group neutralized all the Omicron subvariants with an IC50 value ranging from 1.5 to 503.6 ng/mL; thus, this vaccine could serve as a prophylactic and therapeutic intervention. Given the increasing incidence of COVID-19 cases due to the Omicron variant, RBD from the Omicron strain could serve as a candidate immunogen that can induce higher neutralization activities against the SARS-CoV-2 Omicron sublineages.

| S-EPMC10583637 | biostudies-literature

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

Project description:The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.

| S-EPMC9834171 | biostudies-literature

Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters.

Project description:The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.

| S-EPMC9900747 | biostudies-literature

Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants.

Project description:SARS-CoV-2 variants have posed significant challenges to the hopes of using ancestral strain-based vaccines to address the risk of breakthrough infection by variants. We designed and developed a bivalent vaccine based on SARS-CoV-2 Alpha and Beta variants (named SCTV01C). SCTV01C antigens were stable at 25 oC for at least 6 months. In the presence of a squalene-based oil-in-water adjuvant SCT-VA02B, SCTV01C showed significant protection efficacy against antigen-matched Beta variant, with favorable safety profiles in rodents. Notably, SCTV01C exhibited cross-neutralization capacity against Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5) in mice, superior to a WT (D614G)-based vaccine, which reinforced our previously published findings that SCTV01C exhibited broad-spectrum neutralizing potencies against over a dozen pre-Omicron variants and the Omicron BA.1 variant. In summary, variant-based multivalent protein vaccine could be a platform approach to address the challenging issues of emerging variants, vaccine hesitancy and the needs of affordable and thermal stable vaccines.

| S-EPMC9486464 | biostudies-literature

Effectiveness of Homologous and Heterologous Covid-19 Boosters against Omicron.

Project description: Not available

| S-EPMC9165559 | biostudies-literature

Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB.

Project description: Not available

| S-EPMC9749618 | biostudies-literature