Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein-peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays. Additionally, immunized animals developed mucosal antibodies in bronchoalveolar lavage fluids (BAL). The level of mucosal or serum ADMP and ADNKA antibodies was found to be UB-612 dose-dependent. Our results highlight that the novel subunit UB-612 vaccine is a potent B-cell immunogen inducing polyfunctional antibody responses contributing to anti-viral immunity and vaccine efficacy.
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http://dx.doi.org/10.3390/vaccines12010040 | DOI Listing |
iScience
February 2024
UBI Asia, Hsinchu, Taiwan.
UB-612 pan-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine targets the monomeric Spike S1-receptor binding domain (RBD) subunit protein along with five sequence-conserved T cell epitopes found on Spike S2 and non-Spike M and N proteins. UB-612 vaccination safely induces potent, broad, and long-lasting immunity against SARS-CoV-2. A phase-2 trial-extended observational study during the Omicron BA.
View Article and Find Full Text PDFVaccines (Basel)
December 2023
Vaxxinity, Inc., Merritt Island, FL 32953, USA.
Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein-peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays.
View Article and Find Full Text PDFPLoS Pathog
April 2023
Division of Infectious Diseases, China Medical University Children's Hospital, China Medical University, Taichung, Taiwan.
Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success.
View Article and Find Full Text PDFJ Microbiol Immunol Infect
June 2023
Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan; Department of Laboratory Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan; PhD Program for Ageing, School of Medicine, China Medical University, Taichung, Taiwan. Electronic address:
From January 2020 to December 2022, there was a total of 8,872,955 confirmed COVID-19 cases in Taiwan. In addition, a total of 15,253 COVID-19 related deaths were reported. During these three years, the government and health authority did many efforts to response this pandemic.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2022
Vaxxinity, Inc., Dallas, TX, USA.
The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques.
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