Immune Imprinting, Non-Durable Hybrid Immunity, and Hybrid Immune Damping Following SARS-CoV-2 Primary Vaccination with BNT162b2 and Boosting with mRNA-1273

Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-12...

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Detalles Bibliográficos
Autores: Erice, Alejo, Nuño, Néstor, Prieto, Lola, Caballero, Cristina
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Málaga
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/6315
Acceso en línea:https://hdl.handle.net/10641/6315
Access Level:acceso abierto
Palabra clave:BNT162b2
SARS-CoV-2
SARS-CoV-2 T-cell response
SARS-CoV-2 antibody humoral immune response
SARS-CoV-2 vaccine
immune damping
immune imprinting
mRNA-1273
Immunology
Pharmacology
Drug Discovery
Infectious Diseases
Pharmacology (medical)
SDG 3 - Good Health and Well-being
Journal Article
Yes
yes
Descripción
Sumario:Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-1273 nine months later. Antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike (anti-RBD) were measured at eight time points during follow-up; the SARS-CoV-2-specific T cell response was measured 16 and 25 months after primary vaccination using an interferon-γ release assay. Results: During the 9-month follow up period after primary vaccination and before the mRNA-1273 booster, anti-RBD were significantly higher at all time points in subjects with documented SARS-CoV-2 infection before the first study time point (previously infected subjects; n = 50) compared to naïve subjects (n = 208; p < 0.05). During a 16-month follow up period following the mRNA-1273 booster, anti-RBD were lower at all time points in previously infected subjects (n = 21) compared to naïve subjects (n = 109), although the differences were non-significant. Breakthrough SARS-CoV-2 infections increased over time in both groups, particularly after the mRNA-1273 booster. Most participants had a persistent SARS-CoV-2 specific T cell response regardless of prior infection. Conclusions: These findings suggest a modulating effect of previous SARS-CoV-2 infection on the humoral immune response to mRNA vaccination, a non-durable hybrid immunity following mRNA vaccination in previously infected subjects, and attenuation of the humoral immune response (immune damping) after repeated exposure to SARS-CoV-2 antigens through mRNA vaccination and/or infection.