Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine

Oberhardt, Valerie; Luxenburger, Hendrik; Kemming, Janine; Schulien, Isabel; Ciminski, Kevin; Giese, Sebastian; Csernalabics, Benedikt; Lang‐Meli, Julia; Janowska, Iga; Staniek, Julian; Wild, Katharina; Basho, Kristi; Marinescu, Mircea Stefan; Fuchs, Jonas; Topfstedt, Fernando; Janda, Aleš; Sogukpinar, Oezlem; Hilger, Hanna; Stete, Katarina; Emmerich, Florian; Bengsch, Bertram; Waller, Christiane; Rieg, Siegbert; Sagar,; Böettler, Tobias; Zoldan, Katharina; Kochs, Georg; Schwemmle, Martin; Rizzi, Marta; Thimme, Robert; Neumann‐Haefelin, Christoph; Hofmann, Maike

doi:10.1038/s41586-021-03841-4

Cited by 322 publications

(325 citation statements)

References 26 publications

Supporting

Mentioning

296

Contrasting

Unclassified

Order By: Relevance

“…Several panels of pMHC tetramers were generated using previously published spike epitopes 15,32,34–36 . Combinatorial tetramer staining ( Supplemental Table 2 ) and enrichment were performed as previously described 26,37 . Spike-specific CD8+ T cells identified by tetramer enrichment were subsequently assessed for memory status by CCR7 and CD45RA expression ( Figure 4A ).…”

Section: Resultsmentioning

confidence: 99%

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Sabatino

Mittl

Rowles

et al. 2021

Preprint

View full text Add to dashboard Cite

Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.

show abstract

Section: Resultsmentioning

confidence: 99%

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Sabatino

Mittl

Rowles

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Another limitation is the focus on humoral immunity without data on cellular immunity. It is also possible that individuals without detectable neutralizing antibodies are protected from infection or at least from severe COVID-19 by a cellular immune response [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Humoral Responses after COVID-19 Vaccination in Peritoneal and Hemodialysis Patients over Twelve Weeks

et al. 2021

View full text Add to dashboard Cite

It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited but is greatly needed to individualize and guide (booster) vaccination strategies. In this prospective, multicenter study we measured anti-spike S1 and neutralizing antibodies in 124 hemodialysis patients, 41 peritoneal dialysis patients, and 20 age- and sex-matched healthy controls over 12 weeks after homologous BNT162b2 vaccination. Compared to healthy controls, both hemodialysis and peritoneal dialysis patients had lower anti-S1 IgG antibodies (median (IQR) 7.0 (2.8–24.3) and 21.8 (5.8–103.9) versus 134.9 (23.8–283.6), respectively; p < 0.001 and p < 0.05) and a reduced SARS-CoV-2 spike protein–ACE2 binding inhibition caused by vaccine-induced antibodies (median (IQR) 56% (40–81) and 77% (52–89) versus 96% (90–98), respectively; p < 0.001 and p < 0.01) three weeks after the second vaccination. Twelve weeks after the second vaccination, the spike protein–ACE2 binding inhibition significantly decreased to a median (IQR) of 45% (31–60) in hemodialysis patients and 55% (36–78) in peritoneal dialysis patients, respectively (p < 0.001 and p < 0.05). Peritoneal dialysis patients mounted higher antibody levels compared with hemodialysis patients at all time points during the 12-week follow-up. Individual booster vaccinations in high-risk individuals without seroconversion or rapidly waning neutralizing antibody levels are required and further data on the neutralization of emerging variants of concern in these patients are urgently needed.

show abstract

“…Indeed, several studies have demonstrated that S protein-specific CD8 + T effector cells were detected already only one week after vaccination. Furthermore, CD4 + T helper and memory cells, which ensure long-term protection could be detected up to six months later [93][94][95][96][97][98][99].…”

Section: Mrna Vaccinesmentioning

confidence: 99%

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

et al. 2021

View full text Add to dashboard Cite

Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID‑19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.

show abstract

Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine

Cited by 322 publications

References 26 publications

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Longitudinal Humoral Responses after COVID-19 Vaccination in Peritoneal and Hemodialysis Patients over Twelve Weeks

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

Contact Info

Product

Resources

About