AUTHOR=Mazzoni Alessio , Vanni Anna , Spinicci Michele , Capone Manuela , Lamacchia Giulia , Salvati Lorenzo , Coppi Marco , Antonelli Alberto , Carnasciali Alberto , Farahvachi Parham , Giovacchini Nicla , Aiezza Noemi , Malentacchi Francesca , Zammarchi Lorenzo , Liotta Francesco , Rossolini Gian Maria , Bartoloni Alessandro , Cosmi Lorenzo , Maggi Laura , Annunziato Francesco TITLE=SARS-CoV-2 Spike-Specific CD4+ T Cell Response Is Conserved Against Variants of Concern, Including Omicron JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.801431 DOI=10.3389/fimmu.2022.801431 ISSN=1664-3224 ABSTRACT=

Although accumulating data have investigated the effect of SARS-CoV-2 mutations on antibody neutralizing activity, less is known about T cell immunity. In this work, we found that the ancestral (Wuhan strain) Spike protein can efficaciously reactivate CD4+ T cell memory in subjects with previous Alpha variant infection. This finding has practical implications, as in many countries only one vaccine dose is currently administered to individuals with previous COVID-19, independently of which SARS-CoV-2 variant was responsible of the infection. We also found that only a minority of Spike-specific CD4+ T cells targets regions mutated in Alpha, Beta and Delta variants, both after natural infection and vaccination. Finally, we found that the vast majority of Spike-specific CD4+ T cell memory response induced by natural infection or mRNA vaccination is conserved also against Omicron variant. This is of importance, as this newly emerged strain is responsible for a sudden rise in COVID-19 cases worldwide due to its increased transmissibility and ability to evade antibody neutralization. Collectively, these observations suggest that most of the memory CD4+ T cell response is conserved against SARS-CoV-2 variants of concern, providing an efficacious line of defense that can protect from the development of severe forms of COVID-19.