Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine

Mian Peng; Xiaowen Dou; Xiuming Zhang; Mingchen Yan; Dan Xiong; Ruiwei Jiang; Tong Ou; Aifa Tang; Xiqiu Yu; Feiqi Zhu; Weiqin Li

doi:10.3389/fimmu.2022.938378

Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine

Front Immunol. 2022 Aug 9:13:938378. doi: 10.3389/fimmu.2022.938378. eCollection 2022.

Authors

Mian Peng^{1

2

3}, Xiaowen Dou⁴, Xiuming Zhang⁴, Mingchen Yan⁵, Dan Xiong⁴, Ruiwei Jiang⁴, Tong Ou⁴, Aifa Tang⁶, Xiqiu Yu⁷, Feiqi Zhu⁸, Weiqin Li^{1

2}

Affiliations

¹ The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
² Department of Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
³ Department of Critical Care Medicine, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁴ Medical Laboratory, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁵ Department of Artificial Intelligence and Bioinformatics, Shenzhen Digital Life Research Institute, Shenzhen, China.
⁶ Science and Education Center, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁷ Department of Gastroenterology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
⁸ Department of Neurology, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

Abstract

Background: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected millions of people around the world. Vaccination is a pillar in the strategy to control transmission of the SARS-CoV-2 spread. Immune responses to vaccination require elucidation.

Methods: The immune responses to vaccination with three doses of inactivated SARS-CoV-2 vaccine were followed in a cohort of 37 healthy adults (18-59 years old). Blood samples were collected at multiple time points and submitted to peptide array, machine learning modeling, and sequence alignment analyses, the results of which were used to generate vaccine-induced antibody-binding region (VIABR) immunosignatures (Registration number: ChiCTR2200058571).

Results: Antibody spectrum signals showed vaccination stimulated antibody production. Sequence alignment analyses revealed that a third vaccine dose generated a new highly represented VIABR near the A570D mutation, and the whole process of inoculation enhanced the VIABR near the N501Y mutation. In addition, the antigen conformational epitopes varied between short- and long-term samples. The amino acids with the highest scores in the short-term samples were distributed primarily in the receptor binding domain (RBD) and N-terminal domain regions of spike (S) protein, while in the long-term samples (12 weeks after the 2^nd dose), some new conformational epitopes (CEs) were localized to crevices within the head of the S protein trimer.

Conclusion: Protective antigenic epitopes were revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine inoculation. A third dose results in a new top-10 VIABR near the A570D mutation site of S protein, and the whole process of inoculation enhanced the VIABR near the N501Y mutation, thus potentially providing protection from strains that have gained invasion and immune escape abilities through these mutation.

Keywords: SARS-CoV-2 vaccine; immunosignatures; inactivated; protective antigenic epitopes; three doses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
COVID-19 Vaccines
COVID-19* / prevention & control
Epitopes
Humans
Middle Aged
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Viral Vaccines*
Young Adult

Substances

COVID-19 Vaccines
Epitopes
Spike Glycoprotein, Coronavirus
Viral Vaccines
spike protein, SARS-CoV-2