Your browser doesn't support javascript.
Antibodies to neutralising epitopes synergistically block the interaction of the receptor-binding domain of SARS-CoV-2 to ACE 2.
Pandey, Manisha; Ozberk, Victoria; Eskandari, Sharareh; Shalash, Ahmed O; Joyce, Michael A; Saffran, Holly A; Day, Christopher J; Lepletier, Ailin; Spillings, Belinda L; Mills, Jamie-Lee; Calcutt, Ainslie; Fan, Fan; Williams, James T; Stanisic, Danielle I; Hattingh, Laetitia; Gerrard, John; Skwarczynski, Mariusz; Mak, Johnson; Jennings, Michael P; Toth, Istvan; Tyrrell, D Lorne; Good, Michael F.
  • Pandey M; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Ozberk V; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Eskandari S; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Shalash AO; University of Queensland Brisbane QLD Australia.
  • Joyce MA; University of Alberta Edmonton AB Canada.
  • Saffran HA; University of Alberta Edmonton AB Canada.
  • Day CJ; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Lepletier A; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Spillings BL; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Mills JL; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Calcutt A; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Fan F; Olymvax Biopharmaceuticals Chengdu China.
  • Williams JT; Gold Coast Hospital and Health Service Gold Coast QLD Australia.
  • Stanisic DI; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Hattingh L; Gold Coast Hospital and Health Service Gold Coast QLD Australia.
  • Gerrard J; Gold Coast Hospital and Health Service Gold Coast QLD Australia.
  • Skwarczynski M; University of Queensland Brisbane QLD Australia.
  • Mak J; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Jennings MP; Institute for Glycomics Griffith University Gold Coast QLD Australia.
  • Toth I; University of Queensland Brisbane QLD Australia.
  • Tyrrell DL; University of Alberta Edmonton AB Canada.
  • Good MF; Institute for Glycomics Griffith University Gold Coast QLD Australia.
Clin Transl Immunology ; 10(3): e1260, 2021.
Article in English | MEDLINE | ID: covidwho-1120050
Semantic information from SemMedBD (by NLM)
1. COVID-19 Vaccines STIMULATES Antibodies
Subject
COVID-19 Vaccines
Predicate
STIMULATES
Object
Antibodies
2. Vaccines AUGMENTS Immune response
Subject
Vaccines
Predicate
AUGMENTS
Object
Immune response
3. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
4. Epitopes INTERACTS_WITH diphtheria toxoid vaccin
Subject
Epitopes
Predicate
INTERACTS_WITH
Object
diphtheria toxoid vaccin
5. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
6. COVID-19 Vaccines STIMULATES Antibodies
Subject
COVID-19 Vaccines
Predicate
STIMULATES
Object
Antibodies
7. Vaccines AUGMENTS Immune response
Subject
Vaccines
Predicate
AUGMENTS
Object
Immune response
8. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
9. Epitopes INTERACTS_WITH diphtheria toxoid vaccine, inactivated
Subject
Epitopes
Predicate
INTERACTS_WITH
Object
diphtheria toxoid vaccine, inactivated
10. Blood PART_OF Patients
Subject
Blood
Predicate
PART_OF
Object
Patients
ABSTRACT

OBJECTIVES:

A major COVID-19 vaccine strategy is to induce antibodies that prevent interaction between the Spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2). These vaccines will also induce T-cell responses. However, concerns were raised that aberrant vaccine-induced immune responses may exacerbate disease. We aimed to identify minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy leading to an effective vaccine with reduced risk of inducing immunopathology.

METHODS:

We procured a series of overlapping 20-amino acid peptides spanning the RBD and asked which were recognised by plasma from COVID-19 convalescent patients. Identified epitopes were conjugated to diphtheria-toxoid and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to block the interaction of the RBD and ACE2.

RESULTS:

Seven putative vaccine epitopes were identified. Memory B-cells (MBCs) specific for one of the epitopes were identified in the blood of convalescent patients. When used to vaccinate mice, six induced antibodies that bound recRBD and three induced antibodies that could partially block the interaction of the RBD and ACE2. However, when the sera were combined in pairs, we observed significantly enhanced inhibition of binding of RBD to ACE2. Two of the peptides were located in the main regions of the RBD known to contact ACE2. Of significant importance to vaccine development, two of the peptides were in regions that are invariant in the UK and South African strains.

CONCLUSION:

COVID-19 convalescent patients have SARS-CoV-2-specific antibodies and MBCs, the specificities of which can be defined with short peptides. Epitope-specific antibodies synergistically block RBD-ACE2 interaction.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Clin Transl Immunology Year: 2021 Document Type: Article