A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted.

Safety and efficacy of dendritic cell vaccine for COVID-19 prevention after 1-Year follow-up: phase I and II clinical trial final result

“…However, there is growing evidence that the T-cell response plays a significant role in the elimination of the COVID-19 virus and is thought to play a central role in forming broad-spectrum and long-term immunity ( 24 – 26 ). In this clinical trial, monitoring for up to 28 days showed that vaccine administration could trigger an optimal specific T-cell response to SARS-CoV-2 ( 8 ). Data from phase I also show good induction of humoral responses.…”

“…AEs that occur up to 28 days post-vaccination, based on reported data, are all mild. Non-COVID AE for up to 28 days was reported by 64.5% of phase I subjects and 53.6% of phase II subjects, and there were no significant differences between treatment groups ( 8 ). Similarly, in follow-ups from 1 to 12 months, the total incidence of non-COVID AE in phase I was 35.71% of subjects.…”

“…The short-term AE incidence rate of DC vaccines is lower compared to conventional COVID-19 vaccines ( 8 ). The grade 3 non-COVID AEs for up to 1 year found in other reported COVID-19 vaccine studies was 1.6% ( Table 5 ) ( 13 ).…”

“…In addition, autologous DC–based vaccines loaded with SARS CoV-2 S-protein (AV-COVID-19 or Nusantara vaccine) can induce adequate T-cell immunity well. The vaccine can also form an antibody response ( 8 ). This article will present the safety results during 1-year observations.…”

Significant improvement of systemic lupus erythematosus manifestation in children after autologous dendritic cell transfer: a case report and review of literature

“…The previous study has shown that ex vivo DC incubation with peptides from the S-protein SARS-CoV-2 can elicit an immunogenic response in the body through the response of T cells and B cells. 15,16 However, this case suggests the possibility that the DC vaccine can also control autoimmune through the tolerogenic response of the DC. Several things that need to be considered in future research are the possibility of special conditions or factors that can cause a tolerogenic response from DC introduced to the SARS-CoV-2 S-protein, such as autoimmune conditions triggered after SARS-CoV-2 infection, genetic variations of DC obtained from people with autoimmune diseases, or the use of immunosuppressive agents such as vitamin D3 and glucocorticoid.…”