A novel SARS-CoV-2 Beta RBD DNA vaccine directly targeted to antigen-presenting cells induces strong humoral and T cell responses.

Throughout the COVID-19 pandemic, several variants of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have evolved, affecting the efficacy of the approved COVID-19 vaccines. To address the need for vaccines that induce strong and persistent cross-reactive neutralizing antibodies and T cell responses, we developed a prophylactic SARS-CoV-2 vaccine candidate based on our easily and rapidly adaptable plasmid DNA vaccine platform. The vaccine candidate, referred to here as VB2129, encodes a protein homodimer consisting of the receptor binding domain (RBD) from lineage B.

Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination.

It has been difficult to translate promising results from DNA vaccination in mice to larger animals and humans. Previously, DNA vaccines encoding proteins that target Ag to MHC class II (MHC-II) molecules on APCs have been shown to induce rapid, enhanced, and long-lasting Ag-specific Ab titers in mice. In this study, we describe two novel DNA vaccines that as proteins target HLA class II (HLA-II) molecules.

DNA Vaccines Encoding Antigen Targeted to MHC Class II Induce Influenza-Specific CD8(+) T Cell Responses, Enabling Faster Resolution of Influenza Disease.

Current influenza vaccines are effective but imperfect, failing to cover against emerging strains of virus and requiring seasonal administration to protect against new strains. A key step to improving influenza vaccines is to improve our understanding of vaccine-induced protection. While it is clear that antibodies play a protective role, vaccine-induced CD8(+) T cells can improve protection.

DNA vaccine that targets hemagglutinin to MHC class II molecules rapidly induces antibody-mediated protection against influenza.

New influenza A viruses with pandemic potential periodically emerge due to viral genomic reassortment. In the face of pandemic threats, production of conventional egg-based vaccines is time consuming and of limited capacity. We have developed in this study a novel DNA vaccine in which viral hemagglutinin (HA) is bivalently targeted to MHC class II (MHC II) molecules on APCs.

Targeted idiotype-fusion DNA vaccines for human multiple myeloma: preclinical testing.

Objectives:   A homodimeric fusion DNA vaccine targeting idiotype (Id) to antigen-presenting cells (APC) induced robust tumor protection in a mouse model of multiple myeloma (MM). Similar Id vaccine molecules were generated for four patients with MM with three main objectives: (i) do the vaccine molecules induce bona fide anti-Id immune responses in mice? (ii) does targeting of the vaccine molecules to APC enhance immune responses? (iii) can anti-Id antibodies, generated as by-product in vaccinated mice, be used to establish sensitive assays for complete remission (CR) prior to patient vaccination?

Methods:   Chimeric vaccine molecules targeting patient Id to mouse major histocompatibility complex (MHC) class II molecules were genetically constructed for four patients with MM.

Results:   DNA vaccination of mice with chimeric vaccines targeting patient Id to mouse MHC class II molecules elicited antibodies specific for the patient's myeloma protein.

Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences.

V regions of monoclonal Ig express an exquisite B-cell tumor-specific antigen called idiotype (Id). Id is a weak antigen and it is important to improve immunogenicity of Id vaccines. Chemokine receptors are expressed on antigen-presenting cells (APCs) and are promising targets for Id vaccines.

Induction of central T cell tolerance: recombinant antibodies deliver peptides for deletion of antigen-specific (CD4+)8+ thymocytes.

In order to prevent or ameliorate autoimmune disease, it would be desirable to induce central tolerance to peripheral self-antigens. We have investigated whether recombinant antibodies (Ab) that deliver T cell epitopes to antigen-presenting cells (APC) in the thymus can be used to induce thymocyte deletion. Troybodies are recombinant Ab with V regions specific for APC surface molecules that have T cell epitopes genetically introduced in their C domains.

Cerebrospinal fluid T cell clones from patients with multiple sclerosis: recognition of idiotopes on monoclonal IgG secreted by autologous cerebrospinal fluid B cells.

Due to somatic recombination and hypermutation, Ig variable heavy (V(H)) and light (V(L)) regions contain unique immunogenic determinants, idiotopes (Id), which can stimulate T cells. To address the relevance of this in a human disease, monoclonal IgG (mAb)-secreting B cell clones were established from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS). HLA-DR-restricted CD4(+) T cell lines and clones from CSF of both patients specifically recognized autologous CSF mAb.