HexaPro / Vaxxas - LARVOL DELTA

Display of Native SARS-CoV-2 Spike on Mammalian Cells to Measure Antibody Affinity and ADCC. (PubMed, Bio Protoc) - "A key challenge in this effort is poor spike stability, with most current methods assessing antibody binding using individual domains instead of the intact spike or variants with stabilizing amino acid changes in the ectodomain (e.g., 2P or HexaPro)...Key features • Allows rapid characterization of antibody binding to native SARS-CoV-2 spike on the mammalian cell surface. • Describes analysis of antibody binding to multiple native spike variants without stabilizing mutations • Describes analysis of Fc-mediated antibody-dependent cellular cytotoxicity • Requires transient transfection of Expi293F and 293T cells to assess antibody binding and ADCC, a flow cytometer for antibody binding, and a plate reader for ADCC • Protocol is readily adaptable to other viral fusogens and membrane proteins."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens. (PubMed, NPJ Vaccines) - "The vaccine, when adjuvanted with AS03, was shown to elicit robust neutralizing antibody and CD4 T cell responses in Phase I/II clinical trials, met its primary co-endpoints in a Phase III trial, and has been licensed by multiple regulatory authorities under the brand name SKYCovioneTM. The RBD-NP immunogens and HexaPro trimers, as well as combinations of VOC-based immunogens, elicited comparable levels of neutralizing antibodies against distinct VOCs. Our results demonstrate that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, demonstrating the potential of two-component RBD-NPs as a platform for the development of broadly protective coronavirus vaccines."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Novel Competitive ELISA Utilizing Trimeric Spike Protein of SARS-CoV-2, Could Identify More Than RBD-RBM Specific Neutralizing Antibodies in Hybrid Sera. (PubMed, Vaccines (Basel)) - "In this study, we aimed to develop and optimize conditions of a competitive ELISA to measure serum neutralizing titer, using a recombinant trimeric Spike protein modified to have six additional proline residues (S(6P)-HexaPro) and h-ACE2...Interestingly, when we tested and compared the neutralizing activity of sera from eleven fully vaccinated individuals who subsequently contracted COVID-19 (hybrid sera), we recorded a moderate correlation between the two assays, while higher sera neutralizing titers were measured with sVNA. Our data indicated that the sVNA, as a more biologically relevant model assay that paired the trimeric S(6P) with ACE2, instead of the isolated RBD-ACE2 pairing cPass test, could identify nAbs other than the RBD-RBM specific ones."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers. (PubMed, Front Immunol) - "We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • IFNG

Precise control of digital dental unit to reduce aerosol and splatter production: new challenges for future epidemics. (PubMed, BMC Oral Health) - "To minimize the spread of aerosol and virus in clinics, dentists are supposed to adopt the minimal viable speed of a dental handpiece with limited cooling water during dental procedures. In addition, comprehensive personal protective equipment is necessary for both dental providers and dental assistants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein. (PubMed, J Gen Virol) - "Here, we investigate the cellular responses induced by HexaPro HD-MAP vaccination. We found that delivery via the HD-MAP induces a type one biassed cellular response of much greater magnitude as compared to standard intramuscular immunization."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models. (PubMed, Nat Commun) - "The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo...Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface. (PubMed, iScience) - "One of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Furthermore, the ChAdOx1-vectored HexaPro-stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase I clinical study to evaluate the safety and tolerability of SARS-CoV-2 spike protein (HexaPro) delivered intradermally by a high-density microarray patch (HD-MAP), in healthy adults aged 18 to 50 years. (ANZCTR) - P=N/A | N=44 | Completed | Sponsor: Vaxxas Pty Ltd | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases