We design and develop vaccines, improve production processes for vaccines and prepare drug substances to enable pre-clinical and clinical studies at cGMP-level under our Vaccine Development Pathway or VDP process.

For new vaccine development, we use established blue prints and scalable platform production processes. These are designed according to regulatory requirements, using mathematical models, and are scalable from lab to high-volume production-scale bioreactors. Rationally designed processes are tested in our laboratory facilities using latest ICH-guidelines and insights.

We have long-standing, extensive experience and capabilities in vaccine development, which can be applied to different vaccine concepts. We provide tailored solutions and enable your high-potential candidate vaccine to become ready for market entry. The most critical part of your development program is our commitment to establishing manufacturing ready processes early, in order to enable the most streamlined transition of your program from clinical to large scale manufacturing. At Intravacc, we are focused on speed, simplicity and reproducibility as we develop your candidate vaccine to allow you going into the clinic as soon as possible.



During the discovery phase of the VDP process we select proteins, antigens and peptides that can be safely used in humans for vaccination. At the same time we select the optimal expression system, vaccine platform and make sure that selected components or methodologies are not infringing any patents. If you decide to choose one of Intravacc’s proprietary technologies for your candidate vaccine, the overall development timelines will be shorter, because bioassays and methods as well as safety data of some of these platforms are quite often already available.

We have the following tools available:

  • GMP-compliant Verocell lines for both R&D and all the way to commercial market
  • Homologous and heterologous OMV platform
  • I-boost protein platform
  • Conjugation technology
  • LPS

Process Development

Intavacc’s team has been developing scalable upstream and downstream biomanufacturing for cells, viruses and bacteria for more than 20 years. With expertise that spans a multitude of production processes, including stable and live attenuated viral vaccines, and bacterial vaccines, our people are ready to optimize your vaccine development.

Strain selection and generation

  • For development and improvement of viral or bacterial based vaccines the scientists at Intravacc have extensive experience in structural and translational microbiology in order to design and create the best candidate organism for the candidate vaccine with the highest immunity, potency and production yield.
  • Viral vaccine design includes optimization of both the production cell line, as well as the virus strain for development of inactivated virus, live-attenuated virus, VLP, and alternatives like SRIP, replicons and virus-vectors.
  • Bacterial vaccine design includes inactivated bacteria, toxins, conjugate vaccines, and vaccines against any pathogen using our OMV-platform
  • Antigen selection is performed via bioinformatics or forced evolution, in silico design and subsequent construction. Factors that are taken into account include: optimization of safety, immunogenicity (such as level of expression, epitope optimization), intrinsic antigen stability, intrinsic safe adjuvant (LPS), conservation of the antigen and vaccine yield.
  • To optimize GMP readiness bacterial strains are genetically modified without selection markers present in the final production strain and viral strains are rescued based on their genetic sequence, thereby circumventing the use of clinical isolates that might harbor extraneous viruses.

We have the following tools available:

  1. 1. Cloning, transfection, propagation
  2. 2. Transfection
  3. 3. Deep sequencing
  1. 4. siRNA screen
  2. 5. Crispr/Cas9
  3. 6. Viral vector design
  4. 7. Protein design

Pre Clinical

The pre-clinical work involves the analysis of safety and immunogenicity of concept vaccines, also in relation to the route of administration. With respect to immunogenicity innate, humoral and cellular responses are characterized using both in vitro and in vivo experiments

  • Innate assays include for example assays to investigate PRR activation, DC or PBMC activation or assessment of early cytokine responses in serum.
  • Humoral responses are measured ex vivo and include measuring antibody levels in serum (all subtypes possible), identification immunogenic antigens by 2 dimensional western blotting in combination with mass spectrometry, quantification of antibody producing plasma cells and antigen specific memory B-cells by EliSpot.
  • Cellular responses include DC-T-cell cocultures (activation and polarization of T cells) in vitro and identification of quantity and quality of antigen specific T-cells ex vivo (intracellular cytokines or cytokines in supernatant, proliferation, local versus systemic responses).

USP development

Throughout the years the our highly experiences USP development teams were involved with the development of vaccines transferred to many vaccine manufactures world-wide. Intravacc’s USP expertise covers both bacterial and cell cultivation as well as virus propagation in flasks and bioreactors ranging from 1L up to 200 L. All the processes are optimized and characterized and are fully scalable. Furthermore, our extensive experience in culturing adherent cells on micro carriers from lab to production-scale and molecular techniques can complement your vaccine concept. Our client-dedicated process development facilities for longer term development and characterization programs allow us to offer focused and customized support to your program. Therefore, we can provide you with a cost-efficient and robust development process. From cell and seedlot banking to medium design, fed-batch, batch or continuous cultures in order to increase the yield and viability of the respective vaccine culture.

We have the following tools available:

  • Cell and seedlot banking
  • Medium design
  • Shake flasks
  • Bioreactors 1-200 L volume (glass, stainless steel or disposable)
  • Batch, Fed-batch and continuous cultures
  • Suspension and adherent cell lines using single-use technologies
  • High cell density and product titer cultures
  • Industry standard production platforms

DSP Development

Efficiency is the key for a good downstream process to obtain consistently a pure and high-quality product while recovering as much target antigen as possible. Intravacc’s DSP expertise encompasses all technologies required to process biological substances in order to obtain a pure and stable vaccine or drug substance. From filtration (NFF/TFF), gradient centrifugation and ultracentrifugation, and selective precipitation to chromatographic separations and viral inactivation – the best and most cost effective methods are available to support development, intensification or improvements from lab to pilot-scale and beyond. In addition, our experience in process development for protein, membrane and viral products enables us to maximize the product recovery using our adaptive platforms.

  •  Adaption of state-of-the-art bioprocess purification processes
  •  Many different filtration techniques • (Ultra)centrifugation
  •  Recombinant and wild-type viruses (enveloped and non- enveloped)
  •  Size exclusion and affinity chromatography
  •  Process intermediate stability studies
  •  Polysaccharide purification for conjugate vaccines
  •  OMV and Protein purification

Analytical method development

Our R&D department focuses on developing high quality, stable vaccine products, using state-of-the-art analytical techniques and eight dedicated laboratories. Here, we:

  • develop, improve and validate analytical tests for characterization and quality control of vaccine products,
  • characterize vaccine products, intermediates, seed lots and starting materials,
  • design, develop and improve formulations, delivery systems and adjuvants for vaccines.

With state-of-the-art instruments, such as mass spectrometers, NMR, HPLC and GC systems, biosensor and qPCR instruments at our disposal, we have substantial experience in developing analytical methods for existing and newly developed vaccines. We perform method development, including GMP-compliant method validation, stability studies and consistency in production. We have expertise in the field of antigen characterization, i.e. biophysical and immunochemical analysis of vaccines. We are focusing on the primary protein sequences, chemical modifications and higher-order structures and the stability of antigens, and the accessibility of immune-dominant epitopes. The antigens we work with are highly diverse and include purified live attenuated viruses, inactivated viruses, toxoids, outer membrane vesicles, subunit vaccines, conjugated antigens. In addition, we develop tests to assess the purity and impurities (e.g. host cell proteins and LPS), of a vaccine product, yield, presence of excipients and adjuvants. We have outstanding technical expertise and put a strong focus on our collaboration partners and clients. Flexibility, fast individual response and customer support are a natural part of our daily business.



The quality, potency and safety are key features in the specification of biopharmaceutical drug substances and clinical samples. Therefore, choosing the right assays for determining the consistently high quality of these vaccines is crucial. Assay performance requires highly skilled technicians with a deep understanding of methods and techniques. Our department consists of technicians and scientists with training and experience in the field of analytical chemistry, organic chemistry, biochemistry, life sciences and pharmaceutical sciences. Intravacc is your preferred partner for all aspects of vaccine-related assay development, assay validation, vaccine quality control and method transfer. We have a proven track record in establishing validated methods according to ICH guidelines for quality control of vaccines. Our broad experience stands for quality completion of your testing requirements. We offer a wide range of analytical method development, characterization, validation and analysis services including:

  • Content of drug substances and drug products
    • Mass spectrometry (de novo sequencing)
    • qPCR
    • ELISA
    • Calibration free concentration analysis (biosensor analysis)
    • HPLC
    • GC
    • Protein assays (BCA, Lowry, Peterson and Bradford)
  • Higher Order Structure of proteins and viruses
    • Circular dichroism (secondary structure of proteins)
    • Fluorescence spectroscopy (tertiary structure of proteins)
    • Dynamic Light Scattering (particle size and protein aggregation)
    • Electrophoretic Light Scattering (surface charge of particles)
    • Asymmetric Flow Field-Flow Fractionation – Multi Angle Light Scattering (FFF-MALS)
    • Nanoparticle Tracking Analysis (NTA)
  • Antigenicity
    • Biosensor analysis (Biacore T200)
    • Affinity measurements of antibodies
    • Epitope mapping (biosensor analysis or mass spectrometry)
    • 2D Western blotting (Immunoproteomic profiles)
  • Impurities
    • Host cell proteins content (ELISA – mass spectrometry)
    • LPS identification and quatification (mass spectrometry or GC)
    • Residual DNA concentration (qPCR)
    • Average chain length of residual DNA from mammalian cells (qPCR)
    • Protease activity
    • DNAse activity (gel electrophoresis)
  • Excipient testing
    • NMR
    • GC
    • HPLC
  • Stability testing
    • Accelerated stability studies
    • Real time stability studies
  • Compendial Testing to USP, EP, JP
    • Appearance
    • pH
    • Osmolality
  • •Cell-based bioassay
    • TCID50
    • Virus-neutralization tests
    • Specific toxicity tests on Vero cells



and delivery

We focus on the development of a proper formulation suitable for the intended administration route of a new vaccine, and stable upon storage of the new vaccine product. We design, develop and improve formulations and adjuvants for new vaccine candidates. The stability of new formulations is tested in accelerated, real-time and in-use stability studies using the appropriate set of assays. However, some vaccines are difficult to stabilize in a liquid formulation, especially if these vaccines contain live-attenuated viruses. To solve this, we have the facilities and expertise to develop water-free vaccine products (e.g. by lyophilization or spray-drying). Drying techniques are also applied for the preparation of stable seed lots and reference materials. Furthermore, we are working on products for alternative routes of administration of vaccines than intramuscular administration (e.g. intranasal or mucosal routes).

Our Advantages

  • Quick identification of stable vaccine formulations using preselected excipients.
  • The use of Design of Experiments to improve vaccine formulations.
  • Accelerated stability studies to predict real-time stability
  • Freeze-drying and spray-drying applications
  • Comprehensive characterization of formulated vaccines

Fill and Finish

We offer comprehensive Fill & Finish services for liquid-formulated vaccines. We support the complete fill-and-finish process that is executed by our qualified contractor manufacturing organization. The fill-and-finish process runs from vaccine bulk formulation to QC release of the final vaccine product, and includes aseptic filling, labeling, packaging, QC testing and storage of the final product. We can also provide lyophilization of the vaccine product.

Our solution-driven GMP-compliant processes come with unparalleled flexibility, fully adaptable to the unique needs for our clients.

  • One-stop service- from vaccine bulk formulation to QC release of the final labelled and packed vaccine product, including storage and shipping
  • Regulatory compliance, EMA compliant


Conjugation & adjuvants

Lipopolysaccharides (LPS)

Lipopolysaccharides or LPS have TLR4 activity and differential cytokine inducing properties, which can be exploited for use as an adjuvant in vaccines or for the development of other TLR4-based therapeutics. In addition, they can be used in LPS-containing vaccines such as those based on meningococcal outer membrane vesicles, allowing the fine-tuning of activation of innate immune responses. However they also exhibit endotoxic activity. The scientists at Intravacc have discovered different ways to genetically reduce the toxicity of the LPS while maintaining their adjuvant properties. We have a phenol-free production process as well as a mass spectrometry method in place to determine the detailed composition of the LPS. HEK cells expressing TLR4 and MD-2 (of different species) are available to analyze the activation.



facilities &

At Intravacc we have two GMP facilities on the campus, Intravacc and Building X. We offer pilot GMP production of viral, bacterial and cancer vaccines. A variety of production technologies are available in both single-use and stainless steel bioreactors.

At Intravacc, the GMP cleanrooms (class c) and quality control span 230 sqm. In Building X four labs are available for BSL3 activities (165 sqm). Two of these labs can be used for GMP activities. Through our partnership network we can produce up to 100 million doses of vaccine.

The bioreactor capacity we offer for both GMP facilities are:

  • 1 L single-use
  • 5 L single use
  • 10 L single-use
  • 50 L single-use
  • 70 L single use
  • 100 L stainless steel
  • 200 L stainless steel
  • 1000 L stainless steel through one of our partners

All with corresponding downstream process equipment.


Need more information?

Contact our

A team of 140+ specialists is at your disposal here in Bilthoven. Contact us to see how we can bring your vaccine concept ready for in-human trials.


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