Omicron-specific cytotoxic T-cell responses are boosted following a third dose of mRNA COVID-19 vaccine in anti-CD20-treated multiple sclerosis patients

Abstract

Importance: The 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. Objective: To determine T-cell responses to the Spike (S)-protein of Omicron in anti-CD20 treated patients before and after their third mRNA COVID-19 vaccination Design: Prospective observational monocentric study Setting: Conducted since March 2021 at the University Hospital Geneva Participants: Twenty 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 dose Main outcomes and measures: Quantification 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. Results: S-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 relevance: Vaccinated 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.

Preserved T cell reactivity to the SARS-CoV-2 Omicron variant indicates continued protection in vaccinated individuals

“…Compared to the Wuhan strain, the Omicron variant carries over 35 mutations in the Spike protein. The impact of these mutations on antibody recognition has been shown to be substantial, with a significant loss of neutralizing activity in serum from both convalescent and vaccinated individuals 2,11 . In previous variants, although antibody neutralizing potency was decreased, T cell responses were maintained 4,12 , although some mutations have been shown to affect CD8 T cell recognition 13 .…”

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

“…promoted T-cell responses 52 , while humoral responses were still heavily dependent on the serostatus following the priming regimen, and B-cell dynamics at the time of booster administration 33,[51][52][53] ; In other words, the booster doses did not promote humoral immunization in pwMS on aCD20 who did not seroconvert following priming vaccination, unless their B-cells were reconstituted. Studies among people on aCD20 with diseases other than MS 54,55 support the same conclusion.…”

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

“…Studies on the impact of newer variants on T cells, including Mu and Omicron in particular, are limited or missing (Madelon et al, 2021). If the majority of T cell responses are maintained, memory T cells may play an important role as a second line of defense in light of the substantial escape of Omicron from antibodies.…”