Nasal and Ocular Immunization with Bacteriophage Virus-like Particle Vaccines Elicits Distinct Systemic and Mucosal Antibody Profiles.

: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration.

Immunization Against Polymorphic Membrane Protein D Tetrapeptide Motifs Limits Early Female Reproductive Tract Infection in a Mouse Model.

: (Ct) is a common pathogen causing urogenital, anal, oral, and ocular infections. Although extensive vaccine efforts have been underway for decades, there is no licensed vaccine available to prevent human Ct infection. Polymorphic membrane protein D (PmpD) is a highly conserved protein present on the surface of Ct elementary bodies, suggesting an important role Ct biology.

Two doses of Qβ virus like particle vaccines elicit protective antibodies against heroin and fentanyl.

Opioid overdoses and opioid use disorder (OUD) are major public health concerns. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs.

Pathogenic and Protective Roles of Neutrophils in Infection.

(Ct) is an obligate intracellular pathogen that causes the most commonly diagnosed bacterial sexually transmitted infection (STI) and is a leading cause of preventable blindness globally. Ct infections can generate a strong pro-inflammatory immune response, leading to immune-mediated pathology in infected tissues. Neutrophils play an important role in mediating both pathology and protection during infection.

A two-dose regimen of Qβ virus-like particle-based vaccines elicit protective antibodies against heroin and fentanyl.

Opioid overdoses and the growing rate of opioid use disorder (OUD) are major public health concerns, particularly in the United States. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs.

A bacteriophage virus-like particle vaccine against oxycodone elicits high-titer and long-lasting antibodies that sequester drug in the blood.

Opioid use disorder (OUD) and opioid overdoses are public health emergencies. In 2021, 80,000 opioid overdose associated deaths were reported in the United States. Despite the availability of treatment strategies, including medications for opioid use disorder (MOUD) and naloxone, opioid overdoses continue to increase at an alarming rate.

An Approach for Antigen-Agnostic Identification of Virus-Like Particle-Displayed Epitopes that Engage Specific Antibody V Gene Regions.

Antibody complementarity determining regions (CDRs) participate in antigen recognition, but not all participate equally in antigen binding. Here we describe a technique for discovering strong, specific binding partners to defined motifs within the CDRs of chimeric, engineered antibodies using affinity selection and counter-selection of epitopes displayed on bacteriophage MS2-based virus-like particles (VLPs). As an example, we show how this technique can be used to identify families of VLPs that interact with antibodies displaying the CDRs encoded by the germline precursor of a broadly neutralizing monoclonal antibody against HIV-1.

Streamlined Data Analysis Pipeline for Deep Sequence-Coupled Biopanning Identification of Pathogen-Specific Antibody Responses in Serum.

Deep sequence-coupled biopanning (DSCB) is a powerful tool that couples affinity selection of a bacteriophage MS2 virus-like particle peptide display platform with deep sequencing. While this approach has been used successfully to investigate pathogen-specific antibody responses in human sera, data analysis is time-consuming and complicated. Here, we describe a streamlined data analysis method for DSCB using MATLAB, expanding the potential for this approach to be deployed rapidly and consistently.

Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design.

Dengue virus (DENV) is a global health problem, with over half of the world's population at risk for infection. Despite this, there is only one licensed vaccine available to prevent infection and safety concerns limit immunization to only a subset of individuals. Most dengue virus vaccine efforts attempt to evoke broadly neutralizing antibodies against structural proteins.

Epitope-Based Vaccines against the Major Outer Membrane Protein Variable Domain 4 Elicit Protection in Mice.

(Ct) is the most common bacterial sexual transmitted pathogen, yet a vaccine is not currently available. Here, we used the immunogenic bacteriophage MS2 virus-like particle (VLP) technology to engineer vaccines against the Ct major outer membrane protein variable domain 4 (MOMP-VD4), which contains a conserved neutralizing epitope (TTLNPTIAG). A previously described monoclonal antibody to the MOMP-VD4 (E4 mAb) is capable of neutralizing all urogenital Ct serovars and binds this core epitope, as well as several non-contiguous amino acids.

Immunogenicity and Protective Capacity of a Virus-like Particle Vaccine against Type 3 Secretion System Tip Protein, CT584.

An effective vaccine against is urgently needed as infection rates continue to rise and causes reproductive morbidity. An obligate intracellular pathogen, employs a type 3 secretion system (T3SS) for host cell entry. The tip of the injectosome is composed of the protein CT584, which represents a potential target for neutralization with vaccine-induced antibody.

Expansion and Refinement of Deep Sequence-Coupled Biopanning Technology for Epitope-Specific Antibody Responses in Human Serum.

Identifying the specific epitopes targeted by antibodies elicited in response to infectious diseases is important for developing vaccines and diagnostics. However, techniques for broadly exploring the specificity of antibodies in a rapid manner are lacking, limiting our ability to quickly respond to emerging viruses. We previously reported a technology that couples deep sequencing technology with a bacteriophage MS2 virus-like particle (VLP) peptide display platform for identifying pathogen-specific antibody responses.

Antibodies to Variable Domain 4 Linear Epitopes of the Major Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women.

is an obligate intracellular bacterium. infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for prevention, in part due to gaps in our knowledge of -specific immune responses elicited during human infections.

Assessing Antibody Specificity in Human Serum Using Deep Sequence-Coupled Biopanning.

Affinity selection using phage-display technologies is a powerful tool for identifying the peptide epitopes of monoclonal antibodies. Coupling affinity selection with deep sequencing technologies allows for the broad assessment of selectant populations. Here, we describe a method for using a phage-display platform to assess antibody specificity in human serum.

Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.

Background: Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses.