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Phage Display Screening Pathogen Antigens or Host-Response Markers for Infectious Diseases

Introduction Our Services Applications Our Advantages Popular Services FAQs Resources Related Sections

Introduction

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. From pandemics like COVID-19 to endemic threats such as tuberculosis and malaria, the constant emergence of new pathogens and variants calls for rapid, robust, and high-resolution tools to unravel host-pathogen interactions. Phage display—renowned for its high-throughput selection capabilities and biological relevance—offers unmatched potential in profiling immune responses, mapping epitope landscapes, and isolating novel antigens or antibody targets. Whether the goal is to identify dominant antigens in bacteria, viruses, and parasites or to explore host-derived response signatures, phage display delivers the specificity and scalability modern research demands. At Creative Biolabs, we stand at the forefront of this effort, harnessing the power of phage display technology to accelerate infectious disease research. Our phage display for biomarker discovery services is built on this technology, which is ideally suited for research and allows us to screen millions of molecular interactions simultaneously. Our team has specialized in creating and screening vast phage display libraries to uncover critical molecular targets. Our end-to-end service is designed to help researchers pinpoint two crucial types of targets: the pathogen antigens that trigger an immune response and the host-response biomarkers that define the nature and severity of that response. This dual approach provides a comprehensive molecular snapshot of an infection, paving the way for next-generation medical interventions.

Pathogen Antigens vs. Host-Response Markers

  • Pathogen Antigens: An antigen is any molecule, typically a protein or polysaccharide on the surface of a pathogen, that can be recognized by the host's immune system and trigger a response.
  • Host-Response Biomarkers: The host produces molecules in response to the infection. A key class of such biomarkers is the antibodies the host generates. While many antibodies are protective, some can be non-functional or harmful (autoantibodies).
Discovery Target What It Is Why It's Important Key Applications
Pathogen Antigen A molecule from the pathogen (e.g., viral spike protein). Recognized by the host immune system as "foreign." Diagnostics, Vaccine Development, Therapeutic Targets
Host-Response Marker A molecule from the host (e.g., specific antibodies). Reflects the host's reaction to the pathogen. Prognosis, Patient Stratification, Understanding Pathogenesis

Phage Display: A High-Throughput Method for Biomarker Discovery

How can we find the one crucial antigen among thousands of pathogen proteins, or the one significant antibody among millions in a patient's blood? The answer lies in bacteriophage display, a Nobel Prize-winning technology that provides the necessary scale and precision for this monumental task. A bacteriophage (or "phage") is a virus that infects bacteria. We can use genetic engineering to instruct a phage to display a specific peptide or protein on its outer coat while carrying the genetic code for that peptide/protein inside. A phage display library is a vast collection of such phages, often containing billions of unique variants. Each phage displays a different molecule, making the library an immense resource for finding a binder to virtually any target. For infectious disease research, we primarily use three types of libraries:

The Biopanning Workflow

The core process of screening these massive libraries is called biopanning. It's an elegant in-vitro selection process designed to enrich for the rare phages that bind to a target of interest. This entire cycle is typically repeated 3-5 times. With each round, the washing steps can be more stringent, ensuring that only the highest-affinity binders are selected from the enriched pool. After the final round, individual phage clones are isolated, and the DNA inside is sequenced to identify the peptide or antibody responsible for the binding.

Fig.1 The whole process of phage display biopanning. (OA Literature)Fig.1 Phage display biopanning.1

Our Services: Tailored Screening for Your Research Goals

At Creative Biolabs, we have refined the phage display workflow into a suite of powerful, customizable services to address the key questions in infectious disease research.

Service for the Discovery of Novel Pathogen Antigens

This service is designed to identify immunogenic proteins from a pathogen of interest, which can serve as targets for diagnostics, vaccines, or therapeutics. Key steps are:

  1. Library Construction: We start with a cDNA library constructed from the target pathogen (virus, bacterium, etc.), ensuring comprehensive coverage of its proteome.
  2. Biopanning with Patient Sera: The library is panned against a pool of serum samples collected from patients who have successfully recovered from the infection. The antibodies in this "convalescent serum" act as the bait. Phages displaying proteins that are recognized by these patient antibodies will be captured.
  3. Negative Selection: To ensure specificity, the enriched phages are also screened against serum from healthy individuals. Clones that bind to both pools are discarded, eliminating non-specific binders.
  4. Hit Identification & Validation: The final, particular phage clones are sequenced to identify the pathogen antigens. We then proceed with downstream validation, such as expressing the identified antigen as a recombinant protein and confirming its reactivity with a larger panel of patient samples using ELISA.

Applications:

  • Find diagnostic markers for emerging pathogens where commercial assays are unavailable.
  • Identify novel vaccine candidates for bacteria with high rates of antimicrobial resistance.
  • Discover targets for the development of therapeutic monoclonal antibodies.

Service for Profiling the Host Antibody Response

This service aims to characterize the antibody repertoire produced by the host during an infection, providing deep insights into immunity and pathogenesis. This approach inverts the previous one.

  1. Library Selection: We use a high-diversity peptide library or a pre-made library displaying known human antigens (for autoantibody screening).
  2. Biopanning with Patient Sera: This time, the "bait" is a single serum sample or a pool from a specific patient cohort (e.g., patients with severe disease, patients with post-infectious complications). The "prey" is the peptide library.
  3. Comparative Analysis: We perform parallel screenings using different patient groups (e.g., severe vs. mild disease, vaccinated vs. infected). By comparing the binding profiles, we can identify specific antibody patterns unique to each group.
  4. Epitope Mapping & Biomarker Validation: Sequencing the hits reveals the specific peptide sequences (epitopes) recognized by the antibodies in the patient serum. This can pinpoint the exact part of a pathogen that protective antibodies target or identify the host proteins being attacked by autoantibodies.

Applications:

  • Develop prognostic assays by identifying antibody signatures that predict disease severity.
  • Understand mechanisms of protective immunity by mapping the epitopes of neutralizing antibodies.
  • Uncover autoimmune cross-reactivity triggered by an infection, helping to diagnose and manage long-term complications.

Our Customization Options

Options Available
Library Type Random peptide, phage-scFv, Fab, VHH, or custom synthetic libraries
Target Sample Purified antigen, live pathogen, host serum, PBMCs, CSF, BALF
Screening Strategy In-solution, solid-phase, magnetic beads, cell-based, tissue slice-based
Downstream Analysis ELISA, Western blot, Immunofluorescence, Flow cytometry, Epitope binning, SPR
Output Validated clones, sequences, binding kinetics, and epitope maps

When Should You Use This Service?

  • You're investigating immune responses in infectious disease models
  • You need rapid antigen discovery for vaccine development
  • You aim to profile antibodies in patient serum or mucosal fluid
  • You're exploring strain-specific epitope differences in pathogens
  • You're validating autoimmune phenomena post-infection

Advantages of Working with Creative Biolabs

  • Experience in infectious disease and phage display expertise
  • One-stop platform from library to biomarker validation
  • Custom-tailored screens that are built around your research model, disease type, and sample type
  • High-quality, publication-ready reports
  • Our services comply with non-clinical research standards

Popular Services You Might Be Interested In

The fight against infectious diseases demands innovation and precision. Phage display offers an unparalleled platform for uncovering the critical molecular targets needed to develop the next generation of diagnostics, therapeutics, and vaccines. At Creative Biolabs, we provide a phage display-based screening platform tailored to identify pathogen-derived antigens and host-response markers, accelerating biomarker discovery and therapeutic lead identification. Creative Biolabs has the technology, expertise, and dedication to help you succeed. Contact us today and let's collaborate to accelerate your research.

FAQs

Q: How do I know which phage display library is best for my research?

A: Our team of experts will assist you in choosing the best library based on your research objectives, whether you are studying bacterial, viral, or host markers. We consider factors such as the nature of the pathogen and the type of immune response you want to investigate.

Q: What types of samples can I use for phage display screening in infectious disease research?

A: We accept a broad range of sample types, including purified pathogen antigens, whole-cell lysates, live or inactivated pathogens, as well as host-derived specimens such as serum, plasma, cerebrospinal fluid (CSF), BALF, and PBMCs. All samples are handled following strict biosafety protocols.

Q: Can you help with identifying novel antigens in emerging infectious diseases?

A: Yes. We specialize in working with emerging pathogens by utilizing custom libraries, providing flexibility to target novel antigens. Our platform allows screening against newly discovered pathogens using synthetic peptide libraries or recombinant antigens from gene sequences.

Q: What are the limitations of using phage display in infectious disease research?

A: While phage display is compelling, it may be limited when working with extremely large or complex antigens. Some membrane proteins or highly glycosylated structures may require additional preparation or different display formats to ensure successful binding. We collaborate closely with clients to design the best approach for their specific targets.

Reference:

  1. Tian, Lei, et al. "Phage display for the detection, analysis, disinfection, and prevention of Staphylococcus aureus." Smart Medicine 1.1 (2022): e20220015. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.1002/SMMD.20220015

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