A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

Jonas S Heitmann,Marion Richter,Simon Jäger,Sebastian Hörber,Elke Jäger,Reinhild Klein,Jens Bauer,Helmut R Salih,Andreas Peter,Hans‐Georg Rammensee ,Marcel Wacker,Claudia Tandler,Leonard Anton,Imma Fischer,Yacine Maringer,Monika Denk,Jonas Rieth,Julia Karbach,Malte Roerden,Julia Reusch,Annika Nelde,Tatjana Bilich,Christoph Meisner,Maddalena Marconato,Markus Löffler ,Lisa M Weber ,Juliane S Walz

doi:10.1038/s41586-021-04232-5

Abstract

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18–80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

Highlights

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P proteins[1,2], combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to
Magnitude of CoVac-1-induced CD4+ T-cell responses did not differ between Part I and Part II participants and was up to 40 times higher compared to SARS-CoV-2-specific CD4+ T-cell responses of human COVID-19 convalescents (HCs) (0.42% vs. 0.01% CoVac-1-specific IFN-γ+CD4+ T cells Part II participants vs. HCs respectively, Fig. 2d, Extended Data Fig. 5a)

Summary

23 November 2021

Vaccine-induced IFN-γ T-cell responses were observed in 100% of participants in Part I and Part II on day 28, showing a ≥ 200-fold and ≥ 100-fold increase (median calculated spot counts 2 (day 1) to 450 (day 28) and 2 (day 1) to 325 (day 28)) from baseline, respectively (Fig. 2a). The CoVac-1 peptide P6_ ORF8 derived from the ORF8 of SARS-CoV-2 showed most frequently induced T-cell responses after vaccination (97%), followed by P5_mem and P4_env (both 94%), P3_spi (89%), P1_nuc (61%), and P2_nuc (58%, Extended Data Fig. 2). Intensity of IFN-γ T-cell response decreased ex vivo in Part I participants over time, but equivalent expandability of CoVac-1-induced T cells was observed in both, Part I and Part II participants, at month 3 compared to day 28 post vaccination (Extended Data Fig. 3a). E counts 288 pCoVs B.1.1.7, 485 pCoVs B1.351, 13 HCs WT, 14 HCs B1.1.7, 12 HCs B.1.351, Fig. 3c, Extended Data Fig. 7)

AT Discussion

E Female

E Statistical analysis

D Reporting summary

Findings

Methodology