Investigating cellular responses to COVID-19 vaccination

Thanks to the relentless work of the scientific community, different COVID-19 vaccines have been developed at an enormous speed to fight the pandemic. As more and more people are being vaccinated, researchers are striving to investigate and understand the cellular response after vaccination. See how SARS-CoV-2 PepTivator® Peptide Pools and MACS® Antigens can help.

Studying the T cell response with PepTivator Peptide Pools

Since most COVID-19 vaccines to date are based on the spike glycoprotein (protein S), our PepTivator Peptide Pools based on this protein are the perfect choice for re-stimulation of SARS-CoV-2–specific T cells after vaccination.

Stimulation with SARS-CoV-2 PepTivator Peptide Pools reveals the presence of virus-specific CD4+ T cells after vaccination

Detecting virus-specific CD4+ T cells after COVID-19 vaccination

The example data highlight that stimulation with SARS-CoV-2 PepTivator Peptide Pools reveals the presence of virus-specific CD4+ T cells in a vaccinated donor. After vaccination, spike protein–reactive T cells were detected via stimulation with a mix of PepTivator SARS-CoV-2 Prot_S, Prot_S1, and Prot_S+ or with the single PepTivator SARS-CoV-2 Prot_S Complete. Both, the applied mix of peptide pools as well as SARS-CoV-2 Prot_S Complete alone cover the complete sequence of the mature spike protein and stimulate virus-reactive T cells to a similar extend.  

Scientific publications 

Check out first publications using PepTivator Peptide Pools to investigate T cell responses after COVID-19 vaccination:

  • Au, L. et al. (2021) Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2. Nat. Med.: Epub ahead of print, May 26.
  • Geers D. et al. (2021) SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccines. Sci. Immunol. 6(59): eabj1750.
  • Harrington, P. et al. (2021) Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces neutralizing antibody and polyfunctional T cell responses in patients with CML. medRxiv 2021.04.15.21255482. Unrefereed preprint.
  • Haun, B. K. et al. (2020) CoVaccine HT™ adjuvant potentiates robust immune responses to recombinant SARS-CoV-2 Spike S1 immunization. Front. Immunol.: Epub ahead of print, Oct. 30.
  • Mazzoni, A. et al. (2021) First dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in ex COVID-19 subjects. medRxiv 2021.03.05.21252590. Unrefereed preprint.
  • Nanishi, E. et al.  (2021) Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity. bioRxiv 2021.05.20.444848. Unrefereed preprint.
  • Shroff, R.T. et al. (2021) Immune responses to COVID-19 mRNA vaccines in patients with solid tumors on active, immunosuppressive cancer therapy. medRxiv 2021.05.13.21257129. Unrefereed preprint.
  • Sir Karakus, G. et al. (2021) Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates. Sci. Rep. 11(1): 5804.
  • Silva-Cayetano, A. et al. (2021) A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice. Med (N Y). 2(3): 243–262.e8.
  • Ssemaganda A. et al. (2021) Expansion of tissue-resident CD8+ T cells and CD4+ Th17 cells in the nasal mucosa following mRNA COVID-19 vaccination. bioRxiv 2021.05.07.442971. Unrefereed preprint.

Research applications

After stimulation with PepTivator Peptide Pools, SARS-CoV-2–reactive T cells can be detected and/or isolated for further research, for example: 

  • Monitoring of spike protein–reactive T cell persistence after vaccination and determination of immune protection.
  • Comparison of different vaccines on the level of T cell reactivity towards the spike protein (e.g. mRNA-based vaccines versus vector-based vaccines).
  • Analysis of pre-existing immunity towards AdV, which may affect efficacy of vector-based vaccines: PepTivator AdV5 Penton or PepTivator AdV5 Hexon can be used to stimulate AdV5-reatcive T cells to investigate the effect of AdV immunity in vaccines based on AdV5 vectors.
  • Comparison of T cell reactivity towards the spike protein and other SARS-CoV-2 proteins in order to distinguish vaccine-induced from natural T cell immunity. For the investigation of natural immunity based on SARS-CoV-2 proteins besides the spike protein, PepTivator SARS-CoV-2 Prot_N covering the nucleoprotein or PepTivator SARS-CoV-2 Prot_M covering the membrane protein can be used.
     
Schematic alignment of the spike glycoprotein and different SARS‑CoV‑2 PepTivator Peptide Pools based on this protein

PepTivator Peptide Pools based on the SARS-CoV-2 spike protein

PepTivator Peptide Pools mainly consist of 15-mer peptides with 11-amino-acid overlaps. They can bind to MHC class I as well as MHC class II complexes and thus are suitable for the antigen-specific stimulation of CD4+ and CD8+ T cells. Especially PepTivator Peptide Pools based on the spike protein are relevant for COVID-19 vaccination research:

PepTivator SARS-CoV-2 Prot_S covers predicted immunodominant sequence domains of the spike protein, PepTivator SARS-CoV-2 Prot_S1 spans the complete N-terminal S1 domain, and PepTivator SARS-CoV-2 Prot_S+ a part of the C-terminal S2 domain. Those products are the perfect choice for researchers interested in distinct parts of the spike protein but can also be combined to achieve a full-length coverage. 

Newly available is our PepTivator SARS-CoV-2 Prot_S Complete: It covers the complete sequence of the mature spike protein (omitting the first four amino acids of the N-terminal signal peptide). For your convenience, PepTivator Prot_S Complete is optimized for water solubility and is delivered in one vial. 

Find these PepTivator Peptide Pools based on the spike protein as well as kits for the analysis of SARS-CoV-2–reactive T cells listed under related products below.

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Exploring the antibody and B cell response with MACS Antigens

MACS Antigens for SARS-CoV-2 research enable the investigation of the virus-specific immune response, including antigen-specific B cells and antibodies. As most COVID-19 vaccines are based on the spike glycoprotein (protein S), our recombinant antigens, available for different parts of the spike protein, are perfectly suitable for studying the B cell response after vaccination.

Usage of MACS Antigens to detect spike protein–specific antibodies after vaccination

Detection of SARS-CoV-2–specific antibodies after COVID-19 vaccination 

The example data highlight that MACS Antigens enable the analysis of SARS-CoV-2–specific antibodies upon COVID-19 vaccination with a spike protein–based vaccine.  
Spike protein–specific antibodies were detected in plasmapheresis samples of a vaccinated donor using Recombinant SARS-CoV-2 Spike-Prot (spike monomer) and Recombinant SARS-CoV-2 Spike RBD, whereas Recombinant SARS-CoV-2 Nucleoprotein and Recombinant Human ACE2 served as controls. Analysis of different plasma dilutions of a vaccinated or convalescent donor sample and comparison to the control sample (healthy donor plasma) illustrate the high sensitivity and specificity of MACS Antigens.  

Usage of MACS Antigens to detect spike protein–specific B cells after vaccination

Detection of SARS-CoV-2–reactive B cells after COVID-19 vaccination

To identify spike protein–reactive B cells after COVID-19 vaccination, PBMCs were stained with Recombinant SARS-CoV-2 Spike-Prot (HEK)-Biotin tetramerized on streptavidin-PE and streptavidin-APC. The analysis illustrates that our recombinant spike protein is suited to detect spike protein–reactive B cells in convalescent as well as vaccinated donors. 

Scientific publications

Check out first publications using MACS Antigens to investigate B cell responses after COVID-19 vaccination:

  • Mazzoni, A. et al. (2021) First dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in ex COVID-19 subjects. medRxiv 2021.03.05.21252590. Unrefereed preprint.

Research applications

MACS Antigens can, for example, be used for the following research applications:

  • Monitoring spike protein–reactive B cell and antibody levels after vaccination and investigation of immune protection. 
  •  Evaluation of different COVID-19 vaccines regarding B cell reactivity and antibody response towards the spike protein (e.g. mRNA-based vaccines versus vector-based vaccines ). 
  • Comparison of B cell reactivity towards the spike protein and anti–spike antibody levels for vaccine-induced versus natural immunity. For a comprehensive investigation of the natural immune response, SARS-CoV-2 antigens besides the spike protein can be applied, e.g., MACS Antigens of the nucleoprotein  or envelope protein.    

     
Schematic overview of MACS Antigens for COVID-19 vaccination research 

Relevant MACS Antigens for COVID-19 vaccination research

Especially MACS Antigens based on the spike protein are relevant for COVID-19 vaccination research. We offer spike trimer and spike monomer as well as the receptor binding domain (RBD) and the S1 and S2 domains, all recombinantly expressed and available with or without biotin. 

Find MACS Antigens based on the spike protein as well as kits for the analysis or enrichment of SARS-CoV-2–reactive B cells listed under related products below.

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