Safety and Immunogenicity of Combined DNA-Polyethylenimine and Oral Bacterial Idiotypic Vaccine for Patients with B-Cell Non-Hodgkin Lymphoma: A Pilot Study

We report, in brief, the results of a phase I, non-randomized study of idiotypic DNA vaccination in patients with B-cell non-Hodgkin's lymphoma (ISRCTN31090206). The DNA sequence of lymphoma-derived immunoglobulin variable regions was used as a tumor-specific antigen fused to the potato virus X coat protein. A conjugate of plasmid DNA with polyethylenimine was used for the intramuscular injections, followed by a boost with an oral live-attenuated Salmonella vaccine carrying the same plasmid. The patients with a complete or partial response to previous chemotherapy received one or two courses of vaccination, including four injections at monthly intervals. The vaccine was well tolerated, with low-grade adverse events. The T-cell immune responses were assessed by ELISpot, at last vaccine, one week and one month post-vaccination, and were detected in 11/14 (78.6%) of the patients. In cases of progression requiring chemotherapy, or the presence of a positive MRD after the first course of vaccination, the patients underwent a second course of vaccination. At the end point, 6/19 vaccinated patients had disease stabilization, while 13/19 were in complete remission. The overall survival was 100% at follow-up, of a median of 2.3 years

Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein

The potential of immune-evasive mutation accumulation in the SARS-CoV-2 virus has led to its rapid spread, causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. The huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants has renewed interest in DNA vaccine technology. Here, we report the rapid generation and immunological evaluation of novel DNA vaccine candidates against the Wuhan-Hu-1 and Omicron variants based on the RBD protein fused with the Potato virus X coat protein (PVXCP). The delivery of DNA vaccines using electroporation in a two-dose regimen induced high-antibody titers and profound cellular responses in mice. The antibody titers induced against the Omicron variant of the vaccine were sufficient for effective protection against both Omicron and Wuhan-Hu-1 virus infections. The PVXCP protein in the vaccine construct shifted the immune response to the favorable Th1-like type and provided the oligomerization of RBD-PVXCP protein. Naked DNA delivery by needle-free injection allowed us to achieve antibody titers comparable with mRNA-LNP delivery in rabbits. These data identify the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study