Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency (preprint)

T-cell immunity is central for the control of COVID-19, in particular in patients incapable to mount a humoral immune response. We previously reported on the favorable safety profile and efficacy in terms of induction of SARS-CoV-2-specific T-cell responses by CoVac-1, a peptide-based T-cell activator, composed of SARS-CoV-2 T-cell epitopes derived from various viral proteins, combined with the toll-like receptor 1/2 agonist XS151. We conducted a Phase I/II open-label trial recruiting 54 patients with congenital or acquired B-cell deficiency who received one single subcutaneous dose of CoVac-1. Immunogenicity until day 28 in terms of CoVac-1-induced T-cell responses was the primary endpoint; safety until day 56 was assessed as secondary endpoint. Neither serious nor grade 4 CoVac-1-related adverse events were observed. The expected local granuloma formation was observed in 94% of study subjects, whereas systemic reactogenicity was mostly mild or absent. SARS-CoV-2-specific Tcell responses were induced in 86% of the patients and directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses exceeded spike-specific T-cell responses after vaccination with mRNA vaccines in B-cell deficient patients and also that of immunocompetent COVID-19 convalescents with and without seroconversion. CoVac-1 induces broad and potent T-cell responses in patients with Bcell/antibody deficiency independently of current variants of concern, with a favorable safety profile. Our data warrant advancement to a pivotal Phase II/III safety and efficacy evaluation.

Antibody binding and ACE2 binding inhibition is significantly reduced for the Omicron variant compared to all other variants of concern (preprint)

The rapid emergence of the Omicron variant and its large number of mutations has led to its classification as a variant of concern (VOC) by the WHO. Initial studies on the neutralizing response towards this variant within convalescent and vaccinated individuals have identified substantial reductions. However many of these sample sets used in these studies were either small, uniform in nature, or were compared only to wild-type (WT) or, at most, a few other VOC. Here, we assessed IgG binding, (Angiotensin-Converting Enzyme 2) ACE2 binding inhibition, and antibody binding dynamics for the omicron variant compared to all other VOC and variants of interest (VOI), in a large cohort of infected, vaccinated, and infected and then vaccinated individuals. While omicron was capable of binding to ACE2 efficiently, antibodies elicited by infection or immunization showed reduced IgG binding and ACE2 binding inhibition compared to WT and all VOC. Among vaccinated samples, antibody binding responses towards omicron were only improved following administration of a third dose. Overall, our results identify that omicron can still bind ACE2 while pre-existing antibodies can bind omicron. The extent of the mutations appear to inhibit the development of a neutralizing response, and as a result, omicron remains capable of evading immune control.