eSymposia | Antibodies and Vaccines as Drugs for COVID-19

Jan 13, 2021 ‐ Jan 14, 2021



Sessions

LEAPS Technology peptide vaccines activate T cells to elicit prophylaxis and therapy for SARS-CoV-2

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-EPOSTER-ROSENTHAL-KEN

LEAPS Technology peptide vaccines activate T cells to elicit prophylaxis and therapy for SARS-CoV-2 Ken S. Rosenthal1*, Daniel H. Zimmerman2, Hyesun Jang,3 Ying Huang,3 Ted M. Ross 3. 1Augusta University/University of Georgia Medical Partnership, Athens GA; 2 CEL-SCI Inc. Vienna VA; 3Center for Vaccines and Immunology- University of Georgia, Athens GA. Ligand Epitope Antigen Presentation System (LEAPS) peptide vaccines combine a T cell epitope containing disease related peptide with an immune cell binding ligand (ICBL) to promote immunogenicity and direct the subsequent immune response. Initial studies with peptides from the SARS-CoV-2 nucleoprotein (NP350, NP146), chosen to contain MHC-1 HLA-binding epitopes, were attached to either the J-ICBL to elicit Th1 responses or the DerG-ICBL to elicit Th2 responses. Balb/C mice immunized with either of two different types of LEAPS conjugates elicited IgG antibodies directed to the NP350 but not NP146. However, antibody to the NP protein is not expected to be protective. K18-hACE transgenic C57Bl6 mice were either unvaccinated, injected with adjuvant or vaccinated with a pool of J-NP350 and J-NP146 or a pool of DerG-NP350 and DerG-NP146 either prophylactically twice (-28 and -14 days) or therapeutically, one day post infection and then challenged with 2.2 5x10e+5 pfu/ml SARS-CoV-2 virus intranasally on study day 0. Whereas none of the control or adjuvant treated mice survived beyond day 8 post challenge, 40%-50% of mice prophylactically or therapeutically treated with LEAPS-NP vaccines survived to study end at day 12 and were regaining lost weight. The success of this therapy was statistically significant at a 95% level. These results indicate that LEAPS-peptide activated T cells directed towards the NP can deliver therapeutic protection and that the response to the vaccines is quick enough to elicit therapy from a lethal challenge with SARS-CoV-2.

Speaker(s):
  • Ken S. Rosenthal, PhD, Augusta University/University of Georgia Medical Partnership

Vaccine with novel broad-spectrum immunologic adjuvant to combat COVID-19

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-eposter-feyisa-mulugeta

Vaccine with novel broad-spectrum immunologic adjuvant to combat COVID-19 Vaccine with novel broad-spectrum immunologic adjuvant which can trigger a wide spectrum of immune cells can be used to provide protection against COVID-19. One of the main challenge for COVID-19 vaccine development is lack approved adjuvants which can induce the required responses. In an attempt to solve this problem, I discovered a novel broad-spectrum immunologic vaccine adjuvant which can exhibit immunomodulatory effects on a wide spectrum of immune cells. A novel broad-spectrum immunologic vaccine adjuvant can enhance immune responses by producing more antibodies, improving the function of the phagocytic cells which destroy viruses and modulating neutrophile and monocytes (macrophages) activity. I have given the name ‘Covid Bullet’ for this broad-spectrum immunologic vaccine adjuvant which have antigen pockets on its surface. Covid-bullet (novel broad-spectrum immunologic vaccine adjuvant) with inactivated SARS-CoV-2 virus on its surface can be used as oral vaccine to provide protection against Covid-19 which is the current global problem. Author: Mulugeta Berhanu, D.V.M Ethiopian Agricultural Transformation Agency

Speaker(s):

Multi-Clonal SARS-CoV-2 Neutralization by Antibodies Isolated from Severe COVID-19 Convalescent Donors

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-eposter-freund-natalia

Multi-Clonal SARS-CoV-2 Neutralization by Antibodies Isolated from Severe COVID-19 Convalescent Donors Michael Mor1, Ben A. Croker2 and Natalia T. Freund1 1 Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University, Israel 2 Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA 92093 USA The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe and not mild infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. Our data also investigate synergy between nAb for optimal combination antibody therapy to prevent and treat COVID-19. These data demonstrate that severe COVID-19 is associated with unique BCR signatures and robust multi-clonal neutralizing responses that are relatively frequent in the population.

Speaker(s):

Design and Use of Synthetic Peptides for Detection of Antibodies in Serum or Plasma of Coronavirus Disease 2019 (COVID-19) Patients

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-EPOSTER-KING-RUBYANNE

Design and Use of Synthetic Peptides for Detection of Antibodies in Serum or Plasma of Coronavirus Disease 2019 (COVID-19) Patients Ruby Anne N. King 1, Janice C. Caoili 2, Romulo J. de Castro 3, Salvador Eugenio C. Caoili 1, Fresthel Monica M. Climacosa 1,4 1 Biomedical Innovations Research for Translational Health Science Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila 2 Section of Infectious Diseases, Department of Medicine, Makati Medical Center 3 Center for Informatics, University of San Agustin 4 Department of Medical Microbiology, College of Public Health, University of the Philippines Manila Using publicly available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences of Philippine origin from the GISAID EpiFlu Database, we selected core peptide sequences from the four viral structural proteins and modified them by incorporating cysteine residues at their N- and C-terminal ends, in order to facilitate end-to-end peptide polymerization via disulfide-bond formation and thereby produce synthetic antigens suitable for antibody detection. Here, we report the preliminary results for our peptide M1 (CADSNGTITVEELKKLLEQC), an artificial sequence consisting of an 18-residue wild-type core sequence derived from the SARS-CoV-2 membrane glycoprotein and flanked by cysteine residues. We dissolved crude M1 in dimethyl sulfoxide and diluted the resulting solution with aqueous urea to facilitate disulfide-bond formation between cysteine residues. We then analyzed the reaction products using polyacrylamide gel electrophoresis, which revealed Coomassie blue-stained material of lower average electrophoretic mobility under non-reducing versus reducing conditions that was consistent with polymerization of M1 via intermolecular disulfide-bond formation. We found that polymerized M1 captured antibodies from convalescent COVID-19 patient plasma (CCPP) more efficiently than monomeric M1 in an indirect enzyme-linked immunosorbent assay (ELISA) and that the binding thus observed was blocked by preincubation of the antibodies with M1. We also observed significantly higher average ELISA signal intensity among CCPP samples compared to archived human plasma samples that were collected prior to the onset of human-to-human SARS-CoV-2 transmission. Our results suggest the potential utility of M1 for antibody detection in contexts of immunodiagnosis and immunosurveillance, particularly in settings where vaccination against COVID-19 is expected to induce production of antibodies against the SARS-CoV-2 spike protein rather than the membrane glycoprotein.

Speaker(s):

T-cell epitope-based subunit vaccine design in case of SARS-CoV-2 infection

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-eposter-mishra-seema

T-cell epitope-based subunit vaccine design in case of SARS-CoV-2 infection Seema Mishra Department of Biochemistry School of Life Sciences, University of Hyderabad-500046 India Urgent attention is required to tackle SARS-CoV-2, the causative virus for Covid19, which has created a pandemic. Peptide-based subunit vaccines are considered relatively safer alternative to mRNA or inactivated viral vaccines for an elderly population which are the prime targets. Powerful Immunoinformatics tools have made it plausible to design new vaccine candidates for T cell epitope-based multi-subunit vaccines (1). Utilizing higher HLA-I and HLA-II binding capacities, proteasomal cleavage and TAP transporter-binding efficiency, a candidate epitope set has been enlisted, spread over the SARS-CoV-2 proteome. A high level of promiscuity and immunogenicity were the other criteria being applied and clustering of the cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes provided a further narrowed-down set. Interestingly, a few candidate epitopes in this list were identical in sequence to previous SARS-CoV characterized epitopes, the latter epitopes were found to be recognized in humans and transgenic mouse. Consequently, a ranked list of epitopes was obtained that in addition to being considered as likely candidates, also provided crucial insights into SARS-CoV-2 immunopathological mechanisms (2). This talk will focus on such studies done with a view to design and further utilize these candidate epitopes into a likely effective multi-epitope subunit vaccine after due in vitro MHC-peptide binding, T cell stimulation and in vivo assays. 1. Mishra S, Sinha S. 2006 Prediction and molecular modeling of T cell epitopes derived from placental alkaline phosphatase for use in cancer immunotherapy. J. Biomol. Struct. Dyn. 24, 109–121. (doi:10.1080/07391102.2006. 10507104). 2. Mishra S. 2020 Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV-2. R. Soc. Open Sci. 7 : 201141 ( http://dx.doi.org/10.1098/rsos.201141).

Speaker(s):

Use of a SARS-CoV-2 Surrogate Virus Neutralization Test to predict a SARS-CoV-2 plaque reduction neutralization test value of ≥1:160 in convalescent plasma (CP) from Canadian blood donors.

Jan 13, 2021 12:00am ‐ Jan 13, 2021 12:00am

Identification: EK31-EPOSTER-DREWS-STEVEN

Use of a SARS-CoV-2 Surrogate Virus Neutralization Test to predict a SARS-CoV-2 plaque reduction neutralization test value of ≥1:160 in convalescent plasma (CP) from Canadian blood donors. Steven J. Drews1,2*, Dana V. Devine3,4, Alyssia Robinson5, Janet McManus3, Emelissa Mendoza5, Kathy Manguiat5, Chantale Pambrun6, Michael Drebot5,7, Heidi Wood5, 1. Canadian Blood Services, Edmonton, AB, Canada, 2. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, 3. Canadian Blood Services, Vancouver, BC, Canada, 4. Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, 5. Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada, 6. Canadian Blood Services, Ottawa, ON, Canada, 7. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada Introduction: Canadian Blood Services utilizes a plaque reduction neutralization test (PRNT)50 titer of 1:160 to qualify SARS-CoV-2 CP. Although PRNT50 is the gold-standard for determining SARS-CoV-2 neutralizing antibody titers in CP, it is labor intensive and requires a biosafety level 3 (BSL3) laboratory. The GenScript SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) Kit (Piscataway, NJ) estimates the % neutralizing capacity of plasma more rapidly in a BSL-2. Aim: To identify the sVNT% cut-off (CO) most capable of identifying high-titer CP (i.e. PRNT50 ≥1:160). Methods: In April 2020, plasma specimens were collected as part of an assay qualification process from individuals with either; a self-declared SARS-CoV-2–positive nucleic acid test (NAT), or risk factors and signs/symptoms of COVID-19 disease, ≥2 weeks after cessation of clinical symptoms. PRNT50 and sVNT were done at National Microbiology Laboratory (Winnipeg, MB, Canada. Data was stored (Microsoft Excel; Redmond, WA) and statistically analyzed (GraphPad Prism 5; San Diego, CA). Results: 59 donors were recruited (30 NAT-positive, 29 no NAT). Donor specimens had; median PRNT50 (1:80), median sVNT% (50.1%). Only 42.4% (25/59) of specimens had a PRNT50 ≥1:160. There was an association between PRNT50 and sVNT% (Spearman r: 0.5474 p

Speaker(s):

Combating COVID‑19: Identifying a Potential Drug Candidate for Human Testing in 90 Days

Jan 13, 2021 9:00am ‐ Jan 13, 2021 9:15am

Identification: ek31-esym-session-Barnhart-Bo

Speaker(s):

Antibodies as Drugs for COVID‑19

Jan 13, 2021 9:00am ‐ Jan 13, 2021 11:40am

Identification: _esym-session-antibody-drugs

Co-Chair(s):

Rapid Selection, Characterization and Clinical Development of Fully‑Human Antibodies Against Emerging Infectious Diseases

Jan 13, 2021 9:15am ‐ Jan 13, 2021 9:30am

Identification: ek31-esym-session-Kyratsous-Christos

Speaker(s):

Cross‑Neutralization of SARS‑CoV‑2 by a Human Monoclonal SARS‑CoV Antibody

Jan 13, 2021 9:30am ‐ Jan 13, 2021 9:45am

Identification: ek31-esym-session-Corti-Davide

Speaker(s):
Print Certificate
Completed on: token-completed_on
Print Transcript
Please select the appropriate credit type:
/
test_id: 
credits: 
completed on: 
rendered in: 
* - Indicates answer is required.
token-content

token-speaker-name
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
/
/
token-index
token-content
token-index
token-content