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. 2023 Mar;95(3):e28679.
doi: 10.1002/jmv.28679.

Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern

Javier García-Pérez  1   2 , Mercedes Bermejo  1   2 , Almudena Ramírez-García  3 , Humberto Erick De La Torre-Tarazona  1   2 , Almudena Cascajero  1   2 , María Castillo de la Osa  4 , Paloma Jiménez  1 , Marta Aparicio Gómez  5 , Esther Calonge  1   2   4 , Aránzazu Sancho-López  3 , Concepción Payares-Herrera  3 , Rocio Layunta Acero  3 , Laura Vicente-Izquierdo  3 , Cristina Avendaño-Solá  3 , José Alcamí  1   2   6 , Mayte Pérez-Olmeda  2   4 , Francisco Díez-Fuertes  1   2
Affiliations

Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern

Javier García-Pérez et al. J Med Virol. 2023 Mar.

Abstract

The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.

Keywords: Omicron; hybrid immunity; mRNA-1273; neutralizing antibodies; timing of vaccination.

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