At Creative Biolabs, we offer cutting-edge phage display broadly neutralizing antibody (bNAb) screening services designed to accelerate the discovery of next-generation antiviral candidates. As viruses rapidly evolve, the discovery of antibodies that can neutralize a broad spectrum of viral variants is critical for pandemic preparedness and effective intervention research. Our platform leverages immense library diversity to isolate high-affinity binders targeting conserved viral epitopes that are often elusive to traditional screening methods. For highly difficult or unstable antigens, please refer to our specialized service: Phage Display for Challenging Target Discovery.
Fig.1 Effector functions of HIV-1 broadly neutralizing antibodies (bNAbs): neutralization, ADCP, ADCC, and CDC.1
The rapid mutation rate of RNA viruses, such as Influenza, HIV, and Coronaviruses, presents a formidable challenge to vaccine research and antibody therapeutic discovery. Traditional monoclonal antibodies often target immunodominant but variable regions, leading to viral escape and reduced efficacy against emerging strains. A broadly neutralizing antibody (bNAb) targets conserved regions—such as the hemagglutinin stem or the cryptic sites on a spike protein—that are essential for viral function and less prone to mutation.
However, these conserved epitopes are often immunosilent or sterically occluded by glycans, making them difficult to target using standard immunization techniques. Phage display offers a robust solution by allowing the screening of billions of antibody variants in vitro against specific, engineered antigens. This technology enables precise viral epitope mapping and the selection of rare binders with exceptional breadth and potency, facilitating the identification of candidates for universal vaccines and pan-viral therapeutics.
We construct massive immune phage display libraries derived from convalescent patients (super-neutralizers) or immunized animals (e.g., llamas for VHH, transgenic mice). This captures the natural diversity of the host response, providing a rich pool of high-affinity candidates for infectious disease antibody discovery.
To target conserved but cryptic epitopes, we employ structure-informed panning strategies. These include competitive elution with non-neutralizing antibodies to block immunodominant regions or the use of engineered antigen scaffolds that selectively expose vulnerable sites on viral glycoproteins.
Our platform is optimized to identify true bNAbs. We perform parallel screening against a panel of diverse viral strains or variants. Binders that cross-react with multiple variants are prioritized for downstream characterization, ensuring the discovery of a potent antiviral antibody.
We provide comprehensive validation services, including measuring binding affinity (KD) via SPR/BLI, epitope binning, and in vitro pseudovirus neutralization assays. We act as a full-service neutralizing antibody discovery CRO to validate the in vitro functional potency of your research leads.
We design and produce recombinant viral antigens (e.g., stabilized trimers, stem domains). Concurrently, we construct or select the optimal phage display library (Human scFv/Fab, VHH, or Peptide) tailored for virology research.
We perform 3-4 rounds of selection. Strategies include "negative selection" to remove binders to irrelevant proteins and "alternating antigen panning" (using different viral strains in sequential rounds) to enrich for cross-reactive neutralizing antibodies.
Individual clones are screened by ELISA for binding to the target antigen. Positive hits undergo DNA sequencing to identify unique sequences and are analyzed for diversity and germline usage.
Selected antibodies are expressed and purified. We validate their broad neutralization potential against a panel of viral vectors or pseudoviruses. Final deliverables include purified antibodies, sequence data, and a full report.
Discovery of monoclonal antibodies or antibody cocktails for research into acute viral infections (e.g., SARS-CoV-2, Ebola) or chronic diseases (e.g., HIV, HBV). These binders can be investigated as potential antiviral agents or engineered into bispecific formats for preclinical studies.
Identification of bNAbs facilitates vaccine research by defining the structure of conserved neutralizing epitopes. This "Reverse Vaccinology" approach guides the design of immunogens that can elicit a protective bNAb response in vivo.
Generation of high-affinity binders for the detection of viral antigens in biological samples. Broadly reactive antibodies are particularly useful for developing research-grade diagnostic assays that can detect multiple strains of a virus simultaneously.
A pivotal 2024 review synthesizes recent research advancements in utilizing broadly neutralizing antibodies (bNAbs) in HIV-1 research. The study conducts a comprehensive analysis of clinical trials, revealing that while monotherapy offers only transient viral reduction due to the rapid emergence of escape mutations, combination therapies utilizing two or more bNAbs targeting non-overlapping epitopes (such as the CD4-binding site, V3-glycan, and MPER) demonstrate significantly improved efficacy. These combinations have successfully maintained prolonged viral suppression and delayed viral rebound during analytical treatment interruptions (ATI) in individuals with antibody-sensitive strains.
Fig.2 Targets of anti-HIV-1 broadly neutralizing antibodies (bNAbs) on the envelope spike protein (Env) in clinical trials.1
Despite challenges regarding viral reservoir latency and pre-existing resistance, the authors conclude that optimizing bNAb breadth and potency is critical. The study positions bNAb combination regimens as a potential long-acting alternative to daily antiretroviral therapy (ART) in future therapeutic strategies, offering a pathway toward sustained remission and effective prevention strategies.
Q: What types of viral antigens can be used for screening?
Q: Can you screen for antibodies that cross-react with multiple viruses?
A: Yes. We use specific panning strategies, such as alternating the antigen target in each round of selection (e.g., Strain A in Round 1, Strain B in Round 2), to enrich for antibodies that recognize conserved epitopes shared between the strains.
Q: Do you offer animal immunization services for library construction?
A: Yes. We can immunize animals (mice, rabbits, camelids) with your specific viral antigen to generate an immune library. We also have access to human naïve and synthetic libraries for non-animal approaches.
Q: How long does the screening process take?
A: A typical phage display screening project takes approximately 6-8 weeks, from antigen preparation to the delivery of sequenced and validated binder candidates.
"Our team was struggling to find binders that cross-react with multiple influenza variants. Creative Biolabs’ strategy of alternating antigens during panning was brilliant. We successfully identified a candidate that targets a conserved stem epitope. The pseudovirus neutralization data they provided was solid for our publication."
"Targeting the receptor-binding domain was tricky because of heavy glycan shielding. Their team suggested an epitope masking approach to focus the selection on the cryptic site. It worked better than expected. We received high-affinity antibody sequences that we are now using for our structural biology studies."
"We needed to screen a massive library quickly for a viral vector project. Access to their pre-made naïve libraries saved us months of immunization time. The diversity is impressive—we pulled out several unique clones with nanomolar affinity in just under 8 weeks. Highly efficient service."
"It’s rare to find a CRO that handles everything from VLP production to functional validation so smoothly. The final data was clean, and the epitope binning analysis helped us select the best leads for our reverse vaccinology research. A truly professional partner."
Reference:
Please kindly note that our services can only be used to support research purposes (Not for clinical use).
Creative Biolabs is a globally recognized phage company. Creative Biolabs is committed to providing researchers with the most reliable service and the most competitive price.
