Vaccine Testing from Discovery to Production
One of the key challenges of effectively developing a vaccine is understanding the immune correlates of protection(1,2). Vaccine development leads to improvements in antigen and adjuvant selection and the design of better vectors – all of which contribute to the success of a vaccine candidate, while keeping appropriate safety testing in mind. It requires appropriate pre-clinical models, testing methodologies, and the availability of necessary immunology tools.
We have decades of experience supporting the vaccine industry with a specific and unique range of products and related services. Our global network of scientific, technical, and regulatory experts provides vaccine developers with the right expertise early in the development process to boost productivity, efficiency, and profitability, and get the safest and most effective vaccines to market.
(1) The current challenges for vaccine development. Oyston, Robinson J Med Microbiol. 2012 Jul;61(Pt 7):889-894. doi: 10.1099/jmm.0.039180-0. Epub 2012 Feb
(2) Challenges and responses in human vaccine development. Stefan HE Kaufmann and all. Current Opinion in Immunology Volume 28, June 2014, Pages 18-26
What’s the Best Approach to Designing a Vaccine?
A vaccine is defined as a biological preparation that stimulates active acquired immunity against a certain disease or pathogen by being an agent that represents the disease-causing microorganism. It’s often made from a weakened or killed form of the microorganism, its toxins, or one of its surface protein antigens. Scientists take many approaches to design vaccines against a pathogenic microorganism. These choices are dictated by the nature of pathogen and the infection, as well as practical considerations about the use of the vaccine. Some of the options include live attenuated, inactivated, DNA, and recombinant subunit vaccines.
Our experts are here to help you figure out the best type of vaccine to develop, design the best path to develop it, and manufacturing it – all while being mindful of all necessary regulatory guidelines.
Where Are You in Your Vaccine Development?
Our services and expertise can help clients meet appropriate regulatory requirements around clinical trials by initiating and completing critical phases of preclinical development by designing, performing, and documenting safety tests. We can also support your strategy that covers early development through to market.
Browse our vaccine development services by clicking the tabs below:
It is important to research and eliminate unsuccessful programs through in vitro and in vivo techniques to find your leading candidate. Our unmatched knowledge of animal models, safety testing, infectious diseases, and immunology will help you select the most promising vaccine candidates and provide the information clients need to develop better vaccines.
From Vaccine In Vitro Assays to In Vivo Models
Find the best bacterial models to use in your drug development program, from early in vitro screening assays to identify efficacy, to a range of clinically relevant in vivo models.
In Vitro Immune Profiling Assays for Vaccine and Adjuvants Development
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.
- Screening peptide/antigen/live viruses
- In vitro immunogenicity assays
- Testing of novel adjuvants and antigen delivery vectors
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.
Challenge and Protection Studies for Vaccine and Adjuvants
As the ultimate test of your vaccine, we do vaccine efficacy testing 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, such as influenza models or respiratory syncytial virus models (RSV).
Infection is measured by clinical disease scores, viral titers, bacterial CFU, and histopathology. We also take immunological readouts pre-infection of antibody levels (IgG, IgG1, IgG2a), HAI, CTL, and lung cytokines. Combining clinical disease with immunological readouts gives a direct comparison between immunogenicity and efficacy of your vaccine.
Ex Vivo Read Out:
- Viral titers or bacterial CFU (the extent of bacterial infection can also be monitored in-life using luminescent strains of bacteria via IVIS imaging)
- Cell-based assays
- Cytotoxicity assays
- Immune modulation assays (ELISA, Luminex, FACS, ELISpot)
- Antibody levels
- Cytokines (systemic, tissue specific)
- T cell, B cell, and immune cell subset characterization
Need help to select the optimimal assay between in vitro and in vivo models for your adjuvants and vaccine development?
Vaccine development follows a strict regulatory pathway, of which safety assessment is a critical component. In addition, study designs and interpreting the subsequent data are also important considerations. The type of studies depends on what type of vaccine you’re developing.
It’s important to select a laboratory that can provide key technical expertise and experience in handling these types of products to run these studies successfully and support critical data interpretation. Studies can be conducted in accordance to Good Laboratory Practice (GLP) as applicable:
Vaccine Safety Testing Considerations
Vaccines follow a strict regulatory pathway and the safety assessment is a critical component. The type of studies conducted depend on the vaccine type and it is due to their diversity that they require a case by case approach.
Module 2: Nonclinical Studies
- Efficacy including vaccine immunogenicity testing and CDC-approved quarantine
- Local/systemic studies
- Vector-shedding studies and biodistribution
- Reproductive toxicology
Module 3: CMC Quality and Lot Release Testing
- Potency and dose response
- Neurovirulence safety testing
Speed Up Your Vaccine Efficacy and Safety Testing
There are many components to consider to effectively develop a vaccine. Learn about the regulatory guidelines, study designs, and endpoints you should consider to efficiently and effectively develop your vaccine from discovery to safety assessment.
Additional scientific expertise includes:
- Assessment of neutralizing antibodies - nAb
- Measurement of the humoral and cellular immune response by ELISpot and by flow cytometry (mainly looking at the activation of specific cell types)
- Measurement of specific biomarkers (e.g., CRP, cytokines)
- Infectivity and titer for vaccines
Laboratory Support Products and Services
Want to know how to Speed Up Your Vaccine Efficacy and Safety Testing?
Charles River Laboratories can expedite vaccine development programs from manufacturing for early-phase clinical trials to lot release for commercial products. We have more than 20 years of experience of virus and vaccine manufacturing along with providing the associated testing to ensure product safety and efficacy. These development services are accompanied by our scientific and regulatory experience, which allows us to predict and eliminate potential pitfalls early in development while ensuring compliance with all applicable international regulatory standards.
- Efficacy/challenge studies
- Adjuvant assessment
- In vivo potency assays and safety testing
- Lot release testing
- Immunogenicity and immunopotency assays
- In vivo biosafety testing
- Pyrogenicity/endotoxin/monocyte activation testing (MAT)
- Dose-ranging studies
- Stability studies
- Genetic stability studies
- Tumorgenicity/oncogenicity testing
Have more questions about vaccine manufacturing and support services?
Frequently Asked Questions (FAQs) about Vaccine Development Services
What is a vaccine?
Vaccines are medicinal agents intended to elicit an immune response by increasing antibody production and/or specific T cell responses. It has led to the reduction and eradication of key infectious diseases globally, including smallpox. The first successful case of vaccination was performed by Edward Jenner in 1796. He was the first to observe that individuals who caught cowpox did not contract smallpox, even when coming in direct contact with the disease.
What happens when you receive a vaccine?
An individual that has been vaccinated produces antibodies against the protein antigen that protect him/her from contracting the disease when attacked by the pathogenic microorganism.
What is a subunit vaccine? What are some examples?
This vaccine can compromise a wide range of different type of subunits, typically viral proteins, protein components, or even peptides of pathogens. Other type of subunit vaccines, like toxoids and bacterial polysaccharides, are detailed separately. They are typically safer and can be manufactured in a well-controlled process.
Viral antigens suitable to induce protective immunity against infection can be isolated from viral particles but are increasingly produced using recombinant DNA technologies. Most purified antigens have limited intrinsic immunogenicity so they, as with subunit vaccines, usually need multiple doses and the incorporation of an adjuvant during vaccine development to induce both antibody-mediated and cellular immunity.
Recombinant antigens are produced in yeast, microbial, and mammalian cell lines in well-established processes with a proven safety profile and batch-to-batch consistency.
Some viruses, like human papillomavirus (HPV) or hepatitis B, cannot be grown in in vitro culture systems to high titers, and subunit vaccines, derived through antigen isolation or recombinant technologies, are now preferred for vaccine manufacturing.
What is a viral, or bacterial vector, vaccine?
Live recombinant bacteria or viral vectors effectively stimulate the immune system like natural infections and have intrinsic adjuvant properties. The use of recombinant proteins allows for the targeting of immune responses focused against few protective antigens as platforms to deliver vaccine antigens and as immunotherapeutic agents to specifically target and kill cancer cells. However, one of the main challenges in developing vaccines for these new strategies of immunization consists of designing vaccines that elicit the appropriate kind of immune response to confer immunity, mainly to intracellular pathogens and especially to those that establish chronic, often lifelong, infections.1
Generally, the recombinant antigens that are delivered either as DNA plasmids or subunit proteins are reasonably safe. In contrast, replicating viral vectors are often highly immunogenic, but they also carry the risk of recombination, reversion to virulence, and pathogenesis during vaccine development.
What is a bacterial polysaccharide vaccine?
Vaccines can be composed of polysaccharide (sugar) molecules found on the outside layer of encapsulated bacteria, such as 23 Streptococcus pneumoniae (pneumococcal). There are several challenges to be aware of during this vaccine development, including the behavior of bacterial structure, capsule switching, the immune response of the host, and cost.
What is an inactivated vaccine? What are some examples of inactivated vaccines?
Purified inactivated viruses have been traditionally used for vaccine development, and such vaccines have proven to be safe and effective for the prevention of diseases caused by viruses like influenza virus and poliovirus.
Inactivated viral vaccines contain purified whole bacteria or viruses which have been killed, typically by chemicals like beta-propiolactone or formaldehyde. Inactivated vaccines usually don’t require refrigeration, and they can be easily stored and transported in a freeze-dried form, which makes them more accessible to people in developing countries. Killed vaccines are generally less immunogenic than live attenuated vaccines. As a result, they are commonly administered with an adjuvant (e.g., aluminum salts) to augment their immunogenicity.
A few examples of inactivated viral are influenza viruses, rabies viruses, hepatitis A viruses and whole-cell Bordetella pertussis vaccine.
What is a live attenuated vaccine? What is it used for?
Live attenuated vaccines contain whole bacteria or viruses which have been “weakened” to create a protective immune response, but do not affect healthy people.
Live vaccines tend to create a strong and lasting immune response. However, they aren’t suitable for people with a compromised immune system, either due to drug treatment or underlying illness, because the weakened viruses or bacteria can multiply too quickly and lead to disease.
Live attenuated vaccines against human viral diseases have been amongst the most successful, cost-effective interventions in medical history. This kind of vaccine development functions well for acute diseases such as smallpox, poliomyelitis, and measles. However, it may not function well to treat chronic infections like HIV due to challenges with safety and efficacy.
What is a toxoid vaccine?
A toxoid is an inactivated native toxin that has lost its ability to cause disease but has retained a reduced amount of immunogenicity. Two well-known toxoid vaccines include the diphtheria-derived toxoid and tetanus toxoid. Their reduced immunogenicity means these types of vaccines often require an immunogenic boost with the addition of an adjuvant.
Identifying and assessing the best vaccine adjuvants are key to developing a plan for this vaccine in immunogenicity studies, as well as their safety. The characterization and potency testing of a toxoid vaccine development is critical, including lethal and intradermal challenge studies to ensure inactivation, consistency, and potency. These are key considerations and will be required as part of the quality control batch release, in consideration of European Pharmacopeia and World Health Organization (2013) guidelines.
Efforts have been made worldwide trying to refine these potency tests to reduce the number of animals, and today, a single-species guinea pig study may be conducted (Choi et al., 2018).
Chan Woong Choi a, Jae Hoon Moon b, Jae Ok Kim a, Si Hyung Yoo a, Hyeon Guk Kim c, Jung-Hwan Kim d, Tae Jun Park a, Sung Soon Kim a, Evaluation of Potency on Diphtheria and Tetanus Toxoid for Adult Vaccines by In Vivo Toxin Neutralization Assay Using National Reference Standards. Osong Public Health Res Perspect 2018;9(5):278−282
What is a virus-like particles vaccine?
Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses, but can potentially yield safer and cheaper vaccine candidates due to the lack of a viral genome. VLPs are a high-priority alternative to traditional vaccine development against infectious pathogens due to their safety, simplicity, and favorable immunological characteristics to induce both humoral and cellular immune responses.
Attenuation or inactivation is not required, which is particularly important because epitopes are commonly modified by inactivation treatments. Compared to individual proteins or peptides, VLPs present conformational epitopes more similar to the native virus; therefore, the immune system response is expected to significantly improve. Using molecular biology methods, it is possible to adapt one or more antigens to these multimeric protein structures for broader and more efficient protection.
It's interesting to note that VLPs for HPV include antibody responses that exceed those following natural HPV infections.
What is a messenger RNA/DNA vaccine?
In the past few years, nucleic acid-based vaccines (i.e., DNA [as plasmids] and RNA [as messenger RNA (mRNA)] vaccines, have been studied as a new therapeutic modality. They pave the way for safe and efficacious biologics to mimic inoculation with live organism-based vaccines, particularly for stimulation of cell-mediated immunity.
They have advantages over traditional vaccines in terms of safety, efficacy, and inducing both B and T cell response specificity, but there is a technical challenge associated with DNA and RNA vaccines. Since changes of the encoded protein just alter the sequence of the RNA molecule, leaving its physicochemical characteristics largely unaffected, diverse products can be manufactured using the same established production process without any adjustment, saving time and reducing costs when compared with other vaccine development platforms.