In Vivo and In Vitro Vaccine Development Services
Charles River supports vaccine research and development in both the preclinical and clinical phases of discovery, including in vitro immune profiling, cell biology mechanism of action studies, immunogenicity testing, challenge and protection models, and stability testing. Our unique combination of expertise in immunology and anti-infective studies makes us an ideal partner to support your vaccine research – from identification of potential targets to analysis of the immune response and assessment in an infectious challenge model.
Examples of how we can help you with your vaccine research program include:
In Vitro Immune Profiling
The first step in developing your vaccine will be to determine its immunogenicity in vitro. We can test the ability of your novel vaccine antigens to invoke an immune response with our human and animal cell cultures. Our dedicated cell biology team use state-of-the-art methods to not only assess cell proliferation and activation, but also to characterize the nature of the immune response to your antigens.
Testing of Novel and Adjuvants & Antigen Delivery Vectors
We look at antigen uptake by antigen-presenting cells (APCs) and assess cell activation using a variety of methods, including flow cytometry, cell imaging, and functional assays.
In Vivo Immunogenicity Testing
We can help you take your novel vaccine formulations in vivo; testing their ability to stimulate T- and B-cell responses using different delivery routes. We provide data to help you assess the relative potencies of your different formulations by characterizing and quantifying the antibodies produced, and characterizing the magnitude and the nature of the T-cell response.
Figure 1: Charles River tests the ability of your vaccine to induce specific cytotoxic T-cell responses by determining the frequency of interferon-gamma-producing CD8+ cells in the tissues following vaccination.
Challenge & Protection Studies
As the ultimate test of your vaccine, we test efficacy using a wide range of infection models and have the capacity to develop models specific to your needs. Disease specific models of bacterial and viral infection include;
- Influenza models
- Herpes Simplex Virus 1 models (HSV-1)
- Respiratory syncytial virus models (RSV)
- Clostridium difficile models
- Pseudomonas aeruginosa models
- Staphylococcus aureus/MRSA models
- Group B streptococci models
- Streptococcus pneumoniae models
Infection is measured by; clinical disease scores, viral titres, bacterial CFU, and histopathology. The extent of bacterial infection can also be monitored in-life using luminescent strains of bacteria via IVIS imaging. We also take immunological readouts pre infection of; antibody levels (IgG, IgG1, IgG2a), HAI, CTL, lung cytokines. Combining clinical disease with immunological readouts gives a direct comparison between immunogenicity and efficacy of your vaccine.
Which assays and models can aid my vaccine research and development?
Charles River can support every stage of your vaccine development, from pre-clinical in vitro and in vivo assays, through into the clinical phase. Cells based assays can give a useful first look at the immunogenicity of your vaccine, whilst in vivo models will show whether your vaccine can confer protective efficacy. Charles River’s dual Immunology and Microbiology expertise make use the ideal partner to aid our clients vaccine programs, and speed entry into the clinic.
What are the readouts for in vivo immunogenicity testing?
Mice, rats, rabbits and ferrets can be used to assess immunogenicity in vivo. This is measured by; ELISA/ELISPOT analysis of antibody responses, antibody function (opsonophagocytosis, SBA, virus neutralisation, HAI), T helper cell proliferation and cytokine profiling, Cytotoxic T cell responses (flow cytometry, chromium release) and flow cytometric analysis of cellular activation, Tregulatory cell induction.
What in vivo challenge models should I use?
Charles River regularly run infection models with a large range of pathogens, both bacterial and viral. Any of these can be incorporated into a vaccination study to provide a direct measure of protective efficacy of your vaccine.