Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population

Frontiers in Immunology

Immunology

Yeny Acosta-Ampudia¹  Carolina Ramírez-Santana¹  Daniela Weiskopf²  Alba Grifoni²  José Mateus²  Alessandro Sette³  Beatriz Ariza⁴  Claudia Cecilia Cardozo-Romero⁴  Carlos Gómez-Restrepo⁵  Magda Cepeda⁵  Juliana Cuervo-Rojas⁵  Alexandria Dickson⁶  James D. Brien⁶  Andreu Gazquez⁶  Sandra Liliana Valderrama-Beltrán⁷  Julio César Castellanos⁸  John Mario González⁹  Norma Montoya^1,10  Luisa Murcia-Soriano^1,11  Manuel A. Franco^1,12  Federico Perdomo-Celis^1,12  Juana Ángel^1,12  Fabiola Martel^1,12 

[1] Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario,, Bogotá, Colombia;Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United States;Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United States;Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA, United States;Clinical Laboratory Science Research Group, Clinical Laboratory, Hospital Universitario San Ignacio, Bogotá, Colombia;Department of Clinical Epidemiology and Biostatistics, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia;Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States;Division of Infectious Diseases, Department of Internal Medicine. School of Medicine, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio Infectious Diseases Research Group, Bogotá, Colombia;General Direction, Hospital Universitario San Ignacio, Bogotá, Colombia;Group of Basic Medical Sciences, School of Medicine, Universidad de Los Andes, Bogotá, Colombia;Head Clinical Laboratory Unit, Clínica del Occidente, Bogotá, Colombia;Hospital Universitario Mayor-Méderi, Universidad El Rosario, Bogotá, Colombia;Institute of Human Genetics, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia;

关键词: SARS-CoV-2;    variants;    natural infection;    vaccination;    antibody;    CD4+ T cell;    hybrid immunity;    breakthrough infections;   

DOI  :  10.3389/fimmu.2023.1241038

 received in 2023-06-15, accepted in 2023-07-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.

【 授权许可】

Unknown   
Copyright © 2023 Martel, Cuervo-Rojas, Ángel, Ariza, González, Ramírez-Santana, Acosta-Ampudia, Murcia-Soriano, Montoya, Cardozo-Romero, Valderrama-Beltrán, Cepeda, Castellanos, Gómez-Restrepo, Perdomo-Celis, Gazquez, Dickson, Brien, Mateus, Grifoni, Sette, Weiskopf and Franco