Omicron-specific cytotoxic T-cell responses are boosted following a third dose of mRNA COVID-19 vaccine in anti-CD20-treated multiple sclerosis patients
Authors: Madelon Natacha , Heikkilä Nelli , Sabater Royo Irène , Fontannaz Paola , Breville Gautier , Lauper Kim , Goldstein Rachel , Grifoni Alba , Sette Alessandro , Siegrist Claire-Anne , Finckh Axel , Lalive Patrice H. , Didierlaurent Arnaud M. , Eberhardt Christiane S. 
Published: December 2021

AbstractImportanceThe SARS-CoV-2 variant Omicron escapes neutralizing antibody responses elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third dose of vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses.ObjectiveTo determine T-cell responses to the Spike (S)-protein of Omicron in anti-CD20 treated patients before and after their third mRNA COVID-19 vaccinationDesignProspective observational monocentric studySettingConducted since March 2021 at the University Hospital GenevaParticipantsTwenty adults with multiple sclerosis on anti-CD20 treatment (ocrelizumab) who received their third dose of mRNA COVID-19 vaccine 6 to 7 months after their second vaccination. Intervention: Blood sampling before and one month after the third vaccine doseMain outcomes and measuresQuantification of CD4 and CD8 (cytotoxic) T cells specific for SARS-CoV-2 S-protein of vaccine strain, Delta and Omicron variants, using activation marker induced assay (AIM) and comparing frequencies before and after the third vaccine dose.ResultsS-specific CD4 and CD8 T-cell memory against all variants was maintained in around half of the patients six months after their second vaccination, albeit at lower frequencies against Delta and Omicron variants. A third dose enhanced the number of responders to all variants and significantly increased CD8 T-cell responses. The frequencies of T cells specific to Omicron and Delta remained lower than those specific to the vaccine strain after the boost.Conclusion and relevanceVaccinated MS patients on anti-CD20 treatment show robust T-cell responses that recognize S from the circulating Delta and Omicron variants. Response rates increased after the third dose, demonstrating that a booster dose might improve cytotoxic T-cell mediated protection against severe disease in patients with low humoral response. The clinical relevance of the reduced frequencies of T cells specific to Omicron will need to be monitored in the future.Key pointsQuestionAre T-cell responses to Omicron variant conserved in anti-CD20 treated MS patients after COVID-19 mRNA vaccination?FindingsOmicron Spike-specific CD4 and CD8 T cells were detectable in around half of twenty patients six months after the second COVID-19 vaccine dose, and cytotoxic T-cell responses increased following the third dose. Frequencies of T cells specific against the S-protein of Delta and Omicron were lower compared to the vaccine strain, both before and after boost.MeaningIn anti-CD20-treated MS patients the vaccine-induced T-cell responses are little affected by the mutations carried by Omicron, and a third vaccine dose improves cytotoxic T-cell responses.