COVB Technology Platform - Creative Biolabs

COVB Technology Platform: Modular Preclinical Vaccine Development

Creative Biolabs is at the forefront of immunotherapy innovation with our COVB technology platform. This dual-biological engine is specifically engineered for the preclinical development of next-generation cancer and infectious disease vaccines. By integrating the high-efficiency oncolysis of viral vectors with the potent innate immune stimulation of bacterial chassis, we offer a synergistic solution that enhances antigen presentation, remodels the tumor microenvironment (TME), and amplifies systemic anti-tumor immunity. Our modular approach allows for rapid customization across DNA, RNA, and protein-based payloads to meet diverse research objectives.

Synergistic Mechanisms: Virus meets Bacteria

A Composite Immune Delivery Platform

The COVB platform is not merely a combination of components; it is an integrated system for immune delivery and amplification. The viral arm provides strong immunogenicity and direct cell lysis, releasing tumor-associated antigens (TAAs) for cross-presentation. The bacterial arm serves as a "living adjuvant," inducing Toll-like receptor (TLR) and STING activation, thereby converting "cold" tumors into "hot" environments receptive to checkpoint blockade.

The Heterologous Advantage
By alternating viral and bacterial delivery (heterologous prime-boost), the COVB platform minimizes anti-vector immunity while maximizing the quality of poly-functional CD8+ T cell responses, ensuring long-term protective memory.

Core Preclinical Capabilities:
Engineering of viral vectors (Adenovirus, Vaccinia, HSV, VSV).
Attenuated bacterial chassis (Salmonella, Listeria, E. coli Nissle).
Remodeling the immunosuppressive Tumor Microenvironment.
Evaluation of systemic and mucosal immune durability.

COVB vs. Single-Vector Preclinical Platforms

Key Parameter	Traditional Single-Vector Platform	COVB Technology Platform
Innate Immune Activation	Limited to vector-specific PAMPs.	Synergistic dual TLR/STING stimulation.
Antigen Presentation	Dependent on vector cell tropism.	Enhanced APC cross-presentation via oncolysis.
Anti-Vector Immunity	High risk of neutralization upon repeat use.	Dampened by heterologous modulation.
Tumor Penetration	Varies; limited by stromal barriers.	Deep infiltration via engineered bacterial homing.

Preclinical COVB Vaccine Service Modules

COVB Strategy & Antigen Design

Selection of optimal viral/bacterial combinations for synergistic induction.

Identification of multi-antigenic domains (Mad) and neoantigens.
Optimization of antigen expression cassettes (DNA/mRNA/Protein).
Development of heterologous dosing schedules for in vivo studies.
Antigen conservation analysis and drugability planning.

Oncolytic Virus Engineering

Custom construction and characterization of recombinant viral vectors.

Viral rescue and plaque purification for diverse backbones.
Characterization of lytic potency and host range in vitro.
Quantification of transgene expression via ELISA/Flow Cytometry.
Assessment of viral stability and replication kinetics.

Bacterial Chassis & Adjuvant Engineering

Harnessing engineered bacteria as potent delivery vehicles and adjuvants.

Construction of antigen-secreting or surface-displaying bacteria.
Optimization of bacterial colonization and survival kinetics.
Engineering of PAMP-enhanced bacterial hulls or OMV solutions.
Evaluation of bacterial-mediated innate immune activation.

Hybrid Formulation & Delivery Systems

Developing stabilized, multi-component delivery frameworks.

Parameter screening for viral-bacterial co-formulation.
Development of liquid and lyophilized formulation prototypes.
Optimization of administration routes (Intratumoral, Oral, Systemic).
Characterization of stability, particle size, and release profiles.

Mechanism & Functional Verification

Multi-level assessment of immune-coupling and antitumor responses.

In vitro profiling of DC maturation (CD80/83/86) and T-cell priming.
ELISpot, Flow Cytometry, and Cytokine (Luminex/MSD) profiling.
Characterization of tumor cell killing and bystander immunity.
Assessment of functional antibodies (Neutralization, OPK, SBA).

In Vivo Efficacy & Translational Safety

Confirming therapeutic POC in relevant preclinical models.

Tumor growth inhibition (TGI) and survival analysis in mouse models.
Biodistribution and viral/bacterial clearance kinetics studies.
Assessment of viral shedding risk and tissue histopathology.
Evaluation of immunological memory and tumor re-challenge.

Modular Preclinical COVB Development Workflow

Phase 1 — Strategic Definition & COVB Architecture

Selection of TAAs or neo-epitopes and determination of the ideal viral/bacterial chassis (e.g., VSV-GP combined with attenuated Salmonella). We define the priming and boosting logic tailored to the target disease microenvironment.

Phase 2 — Multi-Load Engineering & Pilot Production

Construction of recombinant viral and bacterial vectors. We verify antigen expression through Western Blot/ELISA and perform small-scale purification and titration (TCID50, CFU) to establish a consistent starting material for evaluation.

Phase 3 — In Vitro Mechanism & Immunogenicity Mapping

Functional assessment of oncolytic activity and bacterial colonization. We map the immune footprint including APC uptake, DC maturation markers, and antigen-specific T cell priming using high-parameter flow cytometry.

Phase 4 — In Vivo POC & Safety Characterization

Verification of therapeutic synergy in syngeneic or humanized mouse models. We evaluate TGI, survival, and immunological memory while simultaneously assessing biodistribution, shedding, and tissue safety to establish a translational baseline.

Phase 5 — Comprehensive Data Integration & Candidate Delivery

Final provision of an integrated data package including batch analysis, COA, and efficacy reports. We offer expert recommendations for next-stage IND-enabling studies based on preclinical outcomes.

Enabling Platforms for COVB Development

Modular Viral-Bacterial Synthesis

A flexible engineering platform allowing rapid insertion of diverse payloads into validated viral (oncolytic) and bacterial (adjuvanting) chassis, ensuring high genetic stability and expression fidelity.

Heterologous Prime-Boost Mapping

Specialized protocols to determine the optimal sequence and route (e.g., i.v. vs. i.m.) of viral and bacterial administration, maximizing poly-functional CTL responses while dampening anti-vector immunity.

High-Parameter Immune Profiling

Integration of 30+ parameter Flow Cytometry, ELISpot, and MSD-based cytokine profiling to provide a high-resolution map of the innate and adaptive immune response induced by COVB candidates.

Why Choose Creative Biolabs for COVB Development?

Dual-Biological Integration

We are one of the few CROs offering integrated expertise across both oncolytic virology and engineered bacterial systems for synergistic vaccine development.

Preclinical Precision

Our platform is optimized for rigorous preclinical validation, utilizing advanced multi-omics and in vivo models to ensure candidate drugability.

Modular Flexibility

From specific oncolytic backbones to unique bacterial hulls, we offer fully customizable modules tailored to your specific therapeutic goals.

End-to-End POC Packages

We provide complete traceability and rigorous QC across every phase, delivering a streamlined data package for your next translational step.

Research Insight: Overcoming Resistance with Heterologous Prime-Boost

Synergy of COVB Components in TME Remodeling

Recent preclinical studies (e.g., Das et al. 2021) have demonstrated that heterologous prime-boost regimens—such as combining a self-adjuvanting protein/bacteria vaccine with an oncolytic virus (VSV-GP)—induce potent anti-tumor immunity in otherwise resistant models.

Enhanced T Cell Quality: The COVB approach (KVK regimen) increases the frequency of poly-functional CTLs (IFN-γ+/TNF-α+/CD107a+) and promotes deep infiltration into immune-excluded tumors.
TME Repolarization: Synergistic activation leads to a drastic decrease in TAM-2 and an influx of CD4+ effector cells, effectively "warming" the tumor environment.
Systemic Protection: The combination of bacterial-mediated innate signals and viral-mediated oncolysis establishes robust immunological memory, preventing tumor relapse and protecting against re-challenge.

Immunosuppressive tumor microenvironment remodeling induced by heterologous prime-boost vaccination.

Fig.1 Remodeling of immunosuppressive tumor microenvironment following heterologous prime-boost vaccination.^1,2

FAQs Regarding COVB Technology Services

This combination leverages synergistic mechanisms: the virus provides direct oncolysis and rapid antigen release, while the bacteria serve as sustained innate adjuvants and TME remodeling agents. This dual approach overcomes the limitations of vector-specific immunity and improves T-cell infiltration into 'cold' tumors.

Yes. Engineered bacteria are ideal for mucosal delivery (e.g., oral or intranasal). We can quantify secretory IgA levels, mucosal resident memory T cells (Trm), and tissue-specific colonization dynamics as part of our preclinical evaluation.

We utilize a heterologous prime-boost strategy (alternating virus and bacteria) and optimize dosing intervals. This approach shifts the immune response from anti-vector CTLs to anti-target T cells, as evidenced by significantly enhanced antitumor-to-antiviral T cell ratios.

We monitor viral shedding (qPCR), bacterial persistence/clearance (CFU), biodistribution across vital organs, and tissue-level safety through comprehensive histopathology. These data points are critical for establishing the safety foundation for future translation.

Absolutely. The modular nature of COVB allows for the rapid insertion of personalized neo-epitopes into viral or bacterial backbones. This is particularly effective for high-mutational-burden tumors where multi-load delivery and TME remodeling are essential for efficacy.