Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine

Abstract

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

High neutralizing antibody levels against SARS-CoV-2 Omicron BA.1 and BA.2 after UB-612 vaccine booster

“…In contrast, after the third booster dose, the neutralizing antibody GMT against Omicron and ancestral strain were 106 and 763 (6.3-fold loss) for BNT162b2 ( 11 ), or 850 and 2423 (2.9-fold loss) for mRNA-1273-50 μg ( 7 ). This additional evidence supports the greater extent of UB-612−elicited neutralizing antibodies across multiple SARS-CoV-2 variants particularly after 3 doses, a differentiation property of UB-612 primarily attributed to its RBD antigenic component ( 15 ).…”

“…Two immunizations with UB-612 were immunogenic and led to seroconversion rate of neutralizing antibody in >90% of vaccine recipients. In these same studies, UB-612 was shown to elicit long-lasting neutralizing antibody titers similar to levels detected in convalescent patients ( 15 ) and B cell and T cell responses against Delta and Omicron variants ( 14 ).…”

“…Data expressed in the reciprocal dilutions for each serum sample and GMT (95% CI) are plotted. Of note, the lower level of antibodies against the ancestral strain compared with those obtained from a similar validated CPE assay performed using the same sera (GMT VNT 50 of 127) ( 15 ) is likely to be assay specific.…”

“…The magnitude and extent of reactivity of the humoral response after the UB-612 booster match those reported for the authorized vaccines, including mRNA-1273. Additionally, UB-612 immunization has been shown to stimulate T-cell responses against conserved S, N, and M Th/CTL peptides, included in the UB-612 vaccine formulation ( 13,14, 22 ), and may provide long-lasting antibody responses ( 15 ) which further differentiates UB-612 from many authorized vaccines. As SARS-CoV-2 continues to evolve, several strategies are being explored to effectively prevent COVID-19 caused by newly emerging SARS-CoV-2 variants, including monovalent variant antigen matching, multivalent, or universal vaccine approaches.…”