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

Fabiola Martel, Juliana Cuervo-Rojas, Juana Ángel, Beatriz Ariza, John Mario González, Carolina Ramírez-Santana, Yeny Acosta-Ampudia, Luisa Murcia-Soriano, Norma Montoya, Claudia Cecilia Cardozo-Romero, Sandra Liliana Valderrama-Beltrán, Magda Cepeda, Julio César Castellanos, Carlos Gómez-Restrepo, Federico Perdomo-Celis, Andreu Gazquez, Alexandria Dickson, James D. Brien, José Mateus, Alba GrifoniAlessandro Sette, Daniela Weiskopf, Manuel A. Franco

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article number1241038
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
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.

Funding

This project was funded by Vicerrectoria de Investigación, Pontificia Universidad Javeriana, Universidad de Los Andes, and Universidad El Rosario, under project No. 120136Q0401200 and No. 120136X0401200. This work was also supported by NIH 4U01CA260541, 3U01CA260541-02S1, 75N93019C00065, 75N93021C00016, as well as grant IV-FPC016 from Hospital Universitario Mayor-Méderi, and Fundacion Bolivar Davivienda. Acknowledgments We thank the study participants. Special thanks to Camila Arbelaez for her collaboration in coordinating the recruitment of donors and processing samples, and to Diana Salgado for her logistics support during the recruitment of participants at HUSI and Catherine Jaller MD and Juan Carlos Santos M.Sc at Universidad de Los Andes. We also thank the clinical staff who supported the recruitment of individuals from the cohorts of Los Andes and El Rosario. The RBDs of the ancestral Wuhan, Gamma, Mu, and Delta variants of SARS-CoV-2 and monoclonal antibodies CR3022 and EY-6A used in the HAT were a kind gift from Dr. Alain Townsend and Dr. Tiong Kit Tan (University of Oxford). The serum sample from an individual with SARS-CoV-2 Gamma infection was a generous gift from Dr. Marcela Mercado, Instituto Nacional de Salud, Colombia. We thank Asociación Colombiana de Inmunología (ACOI) for the financial support for publication.

FundersFunder number
Fundacion Bolivar Davivienda
Hospital Universitario Mayor Méderi
Vicerrectoria de Investigación
National Institutes of Health (NIH)75N93021C00016, IV-FPC016, 3U01CA260541-02S1, 75N93019C00065
National Institutes of Health (NIH)
Universidad de los Andes, Chile
Universidad del Rosario120136X0401200, 120136Q0401200
Universidad del Rosario
Pontificia Universidad Javeriana
Asociación Colombiana de Infectología

    Keywords

    • CD4+ T cell
    • SARS-CoV-2
    • antibody
    • breakthrough infections
    • hybrid immunity
    • natural infection
    • vaccination
    • variants

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint

    Dive into the research topics of 'Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population'. Together they form a unique fingerprint.

    Cite this