A recent 1/2 phase study in the journal Nature Portfolio and published in the Research Square * prepress server showed that a coronavirus 2 (SARS-CoV-2) T cell activator for severe acute respiratory syndrome Peptide-focused, CoVac-1, was effective in people with B-cell deficiency.
Study: Phase I / II assay of a peptide-based COVID-19 T cell activator in patients with B cell deficiency. Image credit: Kateryna Kon / Shutterstock
Fund
The pandemic of coronavirus disease induced by SARS-CoV-2 2019 (COVID-19) led to the invention of numerous vaccines that protect billions of humans from the severe course of the disease, mainly through the generation of humoral immunity or activated by antibodies. T-cell immunity is critical in controlling SARS-CoV-2 infection, especially in people who cannot generate a humoral immune response to a prophylactic vaccination or natural infection. Individuals with inherited B cell deficiency and cancer patients with treatment-related B-cell reduction or disease fall into this category. T cells are crucial for the results of COVID-19 and the maintenance of SARS-CoV-2 immunity, as well as humoral immunity driven by B cells.
CoVac-1, a peptide-based T cell activator consisting of SARS-CoV-2 T cell epitopes obtained from various viral proteins, along with receptor agonist 1 and 2 (TLR 1 / 2) XS151, had a favorable efficacy and safety profile in a phase 1 trial among healthy adults considering the induction of COVID-19-specific T cell responses, according to the authors of the current study. This T cell response was higher than that induced by COVID-19 or currently approved SARS-CoV-2 vaccines.
CoVac-1 includes several human leukocyte antigen (HLA) -DR antigen SARS-CoV-2 T cell epitopes generated from different SARS-CoV-2 proteins, such as nucleocapsid (N), spike (S), membrane (M), wrapper (E), open reading frame 8 (ORF 8). Therefore, CoVac-1 stimulates autonomous T cell immunity of current SARS-CoV-2 (VOC) concern variants.
About the study
In the current study, researchers conducted an open 1/2 phase CoVac-1 experiment that enrolled 54 people with acquired or congenital B cell deficiency who received a single subcutaneous dose of CoVac-1 in Germany. . The main objective of the study was immunogenicity in terms of CoVac-1-induced T cell responses up to day 28; the secondary goal was safety until day 56. In addition to B cell deficiency, half of the patients had a CD4 + T cell count below 500 / µl, which shows the seriousness of immunodeficiency of the trial population.
The team evaluated data from patients’ adverse events. T cell reactions to the six SARS-CoV-2 HLA-DR CoVac-1 T cell epitopes were measured by enzyme-linked immunosorbent point assays (ELISPOT) to determine immunogenicity. T-cell responses were measured in all eligible subjects at baseline / day 1, day 7, 14, and 28 after receiving CoVac-1.
Results
The results of the study showed that 94 patients with acquired or congenital B cell deficiency were examined at three research sites in Germany from July 6, 2021 to January 13, 2022. In addition, administer CoVac-1 to 54 patients, 14 in the safety of Phase 1. shooting and 40 in Phase 2 of the experiment.
CoVac-1-induced T cell responses to Omicron variants and compared to vaccine-induced T cell response or mRNA infection. (a) CoVac-1-specific T cell responses evaluated ex vivo in study patients (day 28) compared to peak T-cell-specific responses prior to CoVac-1 administration in patients after the second or third vaccination with approved mRNA vaccines (n = as indicated). (b) Intensities of P3_spike-induced IFN-g T cell responses evaluated ex vivo in study patients (n = as indicated) before and on day 28 after CoVac-1 administration. (c) Examples of ex vivo ELISPOT assays of a study patient (UPN12), with pre-existing T3_spike T cell responses, for the six CoVac-1 peptides on day 1 (white) and day 28 ( gray). The intensities of IFN-g T cell responses are represented as calculated point counts (mean point count of technical replicates minus the respective negative control). (d) The color-coded mutations described for Omicron SARS-CoV-2 variants are shown together with CoVac-1 (orange) peptides. Positive T cell responses to specific T cell epitope-specific compositions (ECs) and cross-reactions in immunocompetent HC (CoVac-1, EC spec, EC cross, n = as indicated) 10,11 and (f) HC immunocompetent unanswered anti-SARS-CoV-2 antibody response after infection (CoVac-1, EC cross spec., n = as indicated) compared with positive IFN-g T cell responses in study patients evaluated ex vivo (B-CoVs, n = as indicated, day 28). (a, b, e, f) The intensity of IFN-g T cell responses is represented as calculated point counts (mean point count of technical replicates minus the respective negative control). Box charts or combined box line charts show the median with the 25th or 75th percentiles and the min / max whiskers. (c) Bars with mean, SD and unique data points. no, name; EC, epitope composition; HC, convalescent without COVID-19; ORF, open reading frame; pos, positive.
Details of unsolicited and unsolicited adverse events were available to each participant using newspaper cards for 28 days after CoVac-1 administration and safety reviews until day 56. No subject left the study due to side effects. The authors did not observe grade 4 associated with CoVac-1 or significant side effects. Expected local granuloma formation was observed in 94% of study participants. On the other hand, systemic reactogenicity was mostly nonexistent or mild.
On the 28th, selective SARS-CoV-2 T cell reactions were generated in 86% of the subjects and targeted to numerous CoVac-1 peptides, with an average of four out of six peptides identified by the cells. T cells of patients. These responses were not influenced by any current Omicron SARS-CoV-2 mutants and were regulated by polyvalent CD4 + T-helper 1 (Th1) T cells. These Th1 cells were positive for interferon γ (IFN-γ), CD107a, interleukin-2 (IL-2), and tumor necrosis factor (TNF).
According to the subgroup analysis, on the 28th, those with acquired B cell deficiency had higher response rates and percentages of CoVac-1-activated T cells than individuals with congenital B cell deficiency. there was no noticeable variation in the frequency and strength of CoVac-1-generated T cell responses between cancer patients receiving anti-CD20 treatment and those who did not.
In addition, in individuals without B cells and immunocompetent subjects recovered by seroconverted / non-seroconverted COVID-19, CoVac-1-generated T cell responses exceeded S-specific T cell responses after vaccination with messenger ribonucleic acid (mRNA) vaccines. CoVac-1 was also able to improve pre-existing S-specific T cell responses.
None of the participants demonstrated any humoral immune response to SARS-CoV-2 in the inclusion of the research, despite receiving more than two doses of approved COVID-19 vaccines. However, the generation of low-grade SARS-CoV-2 immunoglobulin G (IgG) antibodies was observed in patients with a single dose of CoVac-1, despite continuously negative results in SARS-CoV-2 polymerase chain reactions (PCR) in series. .
Conclusions
The present study reported the immunogenicity, reactogenicity, and safety of CoVac-1 in acquired or congenital B-cell deficient risk cohorts. Even in this drastically immunocompromised sample population, this research verified the excellent safety record and demonstrated robust re-activation of T cell responses after a single dose of CoVac-1.
The authors concluded that with an exceptional safety feature, CoVac-1 elicits broad and robust T cell responses in individuals with antibody / B cell deficiency, regardless of existing SARS-CoV-2 VOCs. Current data support the advancement of CoVac-1 to a fundamental Phase 2/3 efficacy and safety study. Long-term research on the efficacy of phase 2/3 using CoVac-1 to determine what phenotypes and T cell frequencies are needed to help cope with COVID-19 is now being prepared.
* Important news
Preprints with Research Square publish preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.