Lipid nanoparticle-encapsulated DNA vaccine robustly induce superior immune responses to the mRNA vaccine in Syrian hamsters.

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery.

Recombinant lipidated FLIPr effectively enhances mucosal and systemic immune responses for various vaccine types.

Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is an immune evasion protein produced by Staphylococcus aureus, and FLIPr is a potential vaccine candidate for reducing Staphylococcus aureus virulence and biofilm formation. We produced recombinant lipidated FLIPr (rLF) to increase the immunogenicity of FLIPr and showed that rLF alone elicited potent anti-FLIPr antibody responses to overcome the FLIPr-mediated inhibition of phagocytosis. In addition, rLF has potent immunostimulatory properties.

Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy.

Background: Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment.

Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity.

Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants.

Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary.

Intranasal Vaccination With Recombinant Antigen-FLIPr Fusion Protein Alone Induces Long-Lasting Systemic Antibody Responses and Broad T Cell Responses.

A simple formulation is urgently needed for mucosal vaccine development. We employed formyl peptide receptor-like 1 inhibitory protein (FLIPr), an FcγR antagonist secreted by , as a vector to target ovalbumin (OVA) to dendritic cells (DCs) intranasal administration. Our results demonstrate that intranasal administration of recombinant OVA-FLIPr fusion protein (rOVA-FLIPr) alone efficiently delivers OVA to DCs in nasal lymphoid tissue.

A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment.

Formyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In this study, we demonstrate that recombinant survivin-FLIPr fusion protein (rSur-FLIPr) binds to FcγRs, and efficient uptake by dendritic cells in vivo.

Immunodomination of Serotype-Specific CD4+ T-Cell Epitopes Contributed to the Biased Immune Responses Induced by a Tetravalent Measles-Vectored Dengue Vaccine.

Dengue is an emerging mosquito-borne disease, and the use of prophylactic vaccines is still limited. We previously developed a tetravalent dengue vaccine (rMV-TDV) by a recombinant measles virus (MV) vector expressing envelope protein domain III (ED3). In this study, we used dengue-susceptible AG129 mice to evaluate the protective and/or pathogenic immune responses induced by rMV-TDV.

Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice.

Background: The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed.

Delivery of Antigen to CD8 Dendritic Cells by Fusing Antigen With Formyl Peptide Receptor-Like 1 Inhibitor Protein Induces Antitumor Immunity.

A major challenge for vaccine development is targeting antigens to dendritic cells (DCs) , enabling cross-presentation, and inducing the memory responses. Fcγ receptors (FcγRs) are expressed on many cell types including DCs. Therefore, targeting of antigen to DCs via FcγRs is an attractive strategy for vaccine development.

Efficient Uptake of Recombinant Lipidated Survivin by Antigen-Presenting Cells Initiates Antigen Cross-Presentation and Antitumor Immunity.

Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic.

Immunogenicity of a novel tetravalent vaccine formulation with four recombinant lipidated dengue envelope protein domain IIIs in mice.

We developed a novel platform to express high levels of recombinant lipoproteins with intrinsic adjuvant properties. Based on this technology, our group developed recombinant lipidated dengue envelope protein domain IIIs as vaccine candidates against dengue virus. This work aims to evaluate the immune responses in mice to the tetravalent formulation.

Recombinant lipidated dengue-3 envelope protein domain III stimulates broad immune responses in mice.

The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope protein domain III (D3ED III) in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-3 envelope protein domain III (LD3ED III) augments the expression levels of IL-12 family cytokines.

The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.

Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost).

Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity.

The combination of recombinant protein antigens with an immunostimulator has the potential to greatly increase the immunogenicity of recombinant protein antigens. In the present study, we selected the dengue-4 envelope protein domain III as a dengue vaccine candidate and expressed the protein in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-4 envelope protein domain III folded into the proper conformation and competed with the dengue-4 virus for cellular binding sites.

Lipidated dengue-2 envelope protein domain III independently stimulates long-lasting neutralizing antibodies and reduces the risk of antibody-dependent enhancement.

Background: Dengue virus is a mosquito-transmitted virus that can cause self-limiting dengue fever, severe life-threatening dengue hemorrhagic fever and dengue shock syndrome. The existence of four serotypes of dengue virus has complicated the development of an effective and safe dengue vaccine. Recently, a clinical phase 2b trial of Sanofi Pasteur's CYD tetravalent dengue vaccine revealed that the vaccine did not confer full protection against dengue-2 virus.

Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III.

Many attempts have focused on the use of either immunomodulators or antigen delivery systems to obtain an efficacious vaccine. Here, we report a novel approach that combined an immunomodulator and delivery system to enhance antigen association and induce robust immunity. We expressed a recombinant lipidated dengue-1 envelope protein domain III (LD1ED III) and its non-lipidated form, D1ED III, in an Escherichia coli system.

A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates.

We have previously demonstrated that vaccination with a subunit dengue vaccine containing a consensus envelope domain III with aluminum phosphate elicits neutralizing antibodies against all four serotypes of dengue virus in mice. In this study, we evaluated the immunogenicity of the subunit dengue vaccine in non-human primates. After vaccination, monkeys that received the subunit vaccine with aluminum phosphate developed a significantly strong and long-lasting antibody response.

Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III.

An anti-IgE monoclonal antibody that binds to IgE on CD23 but not on high-affinity IgE.Fc receptors.

A new monoclonal antibody (mAb), specific for human IgE, the central mediator of immediate-type hypersensitivity reactions, has been shown to possess a unique set of binding specificities. The mAb, 8D6, binds to a conformational epitope on the CH3 domain of human e immunoglobulin and can compete with omalizumab for binding to IgE. Like omalizumab, it does not bind to IgE bound by the high-affinity IgE.

A novel single-dose dengue subunit vaccine induces memory immune responses.

To protect against dengue viral infection, a novel lipidated dengue subunit vaccine was rationally designed to contain the consensus amino acid sequences derived from four serotypes of dengue viruses. We found that the lipidated consensus dengue virus envelope protein domain III (LcED III) is capable of activating antigen-presenting cells and enhancing cellular and humoral immune responses. A single-dose of LcED III immunization in mice without extra adjuvant formulation is sufficient to elicit neutralizing antibodies against all four serotypes of dengue viruses.

Modulation of Epstein-Barr virus latent membrane protein 1 activity by intrabodies.

Objective: The Epstein-Barr virus (EBV) has been implicated in the development of many human neoplasias including B lymphoma and nasopharyngeal carcinoma. EBV latent membrane protein 1 (LMP1) is essential to virus-induced B cell immortalization and the downregulation of cell adhesion molecules that increases cell motility. Therefore, identifying LMP1 activity modulation methods may lead to the development of new therapies for LMP1-positive tumors.

Functional epitopes on porcine endogenous retrovirus envelope protein interacting with neutralizing antibody combining sites.

Porcine cell and organ transplantation provides promise for maintaining normal physiological conditions in patients with end-stage organ failure. The approach however poses serious risk of transmitting pig pathogens to humans. Among many potential pathogens, porcine endogenous retroviruses (PERV) are of particular concern due to their ubiquitous nature in pigs and capability of infecting human cells.

Characterization of a monoclonal antibody specific to the Gag protein of porcine endogenous retrovirus and its application in detecting the virus infection.

The porcine endogenous retrovirus (PERV) has drawn extensive attention recently, due to the widespread use of biomaterials of porcine origin in organ transplantation. This virus is present in all pig strains and has been demonstrated to be capable of infecting human cells in vitro. Therefore, it is imperative to develop a highly sensitive and specific immunoassay for clinical surveillance in patients receiving xenotransplantation.