Abstract

We describe the results of two vaccinations of a self-experimenting healthy volunteer with SARS-CoV-2-derived peptides performed in March and April 2020, respectively. The first set of peptides contained eight peptides predicted to bind to the individual’s HLA molecules. The second set consisted of ten peptides predicted to bind promiscuously to several HLA-DR allotypes. The vaccine formulation contained the new TLR 1/2 agonist XS15 and was administered as an emulsion in Montanide as a single subcutaneous injection. Peripheral blood mononuclear cells isolated from blood drawn before and after vaccinations were assessed using Interferon-γ ELISpot assays and intracellular cytokine staining. We detected vaccine-induced CD4 T cell responses against six out of 11 peptides predicted to bind to HLA-DR after 19 days, following vaccination, for one peptide already at day 12. We used these results to support the design of a T-cell-inducing vaccine for application in high-risk patients, with weakened lymphocyte performance. Meanwhile, an according vaccine, incorporating T cell epitopes predominant in convalescents, is undergoing clinical trial testing.

Highlights

  • After the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), was first sampled and described in December 2019 inWuhan, China [1] and declared a pandemic by the World Health Organization on 11 March2020 [2], the global scientific community responded to this urgency in several resourceful ways

  • Vaccination using Montanide [10,20] or when further adding XS15 as an adjuvant [10], a granuloma developed in both cases

  • The images representing the ELISpot wells were rearranged for this illustration. (B) Graph of spot numbers for the three SARS-CoV-2-derived human leukocyte antigen (HLA)-DR peptides

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Summary

Introduction

After the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), was first sampled and described in December 2019 inWuhan, China [1] and declared a pandemic by the World Health Organization on 11 March2020 [2], the global scientific community responded to this urgency in several resourceful ways. After the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), was first sampled and described in December 2019 in. Hitherto unapproved approaches and vaccine platforms initially intended for immune oncology applications and other diseases were swiftly repurposed, which enabled the development of COVID-19 vaccines at an unprecedented pace [3,4]. Various vaccines to prevent COVID-19 are approved and are available all over the world. Appropriate vaccines for inducing T cell responses are still lacking. For most approved vaccines, evaluations of immune correlates for protection primarily focused on humoral immune responses, providing only very limited data on T cell induction [5]. For specific patient groups, the hitherto available vaccines might demonstrate only limited efficacy or require additional T cell induction, e.g., in patients with B cell malignancies treated with depleting antibodies

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