Vaccine Formulation Development
As specialists in pharmaceutical formulations, BOC Sciences provides you with formulation development and production solutions for inactivated virus vaccines, recombinant protein vaccines, nucleic acid vaccines, live vector vaccines, toxoid vaccines, polysaccharide conjugate vaccines, and peptide vaccines.
What are vaccine?
Vaccines are biologics used to prevent disease. Vaccines activate the body's immune system by introducing parts or all of a pathogen, causing it to produce antibodies and memory cells that target specific pathogens. This way, when real pathogens invade, the immune system is able to quickly recognize and destroy them, thereby preventing disease from occurring. According to the preparation method of vaccines and the use of different objects, vaccines can be divided into a variety of types, including live virus vaccines, recombinant protein vaccines, nucleic acid vaccines, live carrier vaccines, toxoid vaccines, polysaccharide conjugate vaccines, peptide vaccines.
Protein vaccine characterization
Compared with traditional small molecule drugs, the active ingredients of peptide vaccines, recombinant protein vaccines and other biological products have highly complex molecular structures, multiple degradation mechanisms, and lack of effective analytical tools, which makes the development of vaccine formulation technology more challenging. BOC Sciences provides a variety of physicochemical characterization techniques for characterizing the primary and higher structure, post-translational modification, conformational thermal stability, and aggregation tendency of antigen proteins to provide the basis for vaccine formulation development.
| Detection method | Detection parameters and results | Detection method | Detection parameters and results |
| Intact protein mass spectroscopy | Analysis of intact protein primary sequence under reducing conditions, calculation of average molecular weight. | Sedimentation velocity analytical ultracentrifugation (SV-AUC) | Analysis of the size of the antigen protein particles, analysis of the presence of aggregates (monomers, dimers). |
| LC-MS peptide mapping | Peptide mapping analysis, confirmation of the primary sequence of the antigen protein, identification of post-translational modifications. | Hydrophobic interaction chromatography (HIC) | Detection of the hydrophobicity of the antigen protein. |
| Fourier-transform infrared (FTIR) spectroscopy | Analysis of the secondary structure composition of the antigen protein. | Reversed-phase high pressure chromatography analysis (RP-HPLC) | Verification of HIC results. |
| Far-UV circular dichroism spectroscopy (CD) | Analysis of the secondary structure composition of the antigen protein. | Intrinsic tryptophan fluorescence spectroscopy | Tertiary structural thermal stability. |
| Intrinsic tryptophan fluorescence spectroscopy (IF) | Comprehensive analysis of the tertiary structure of the antigen protein. | Differrential scanning calorimetry (DSC) | Tertiary structural thermal stability. |
Vaccine formulation process development
Pre-formulation study
It includes biochemical analysis of biomacromolecules, amino acid sequencing, establishment of analysis methods for stability indexes, and analysis of biophysical properties under pH and ionic strength. These studies contribute to the in-depth understanding of the degradation pathways of biomolecules, so that the ideal excipients and protectants can be selected to meet the specific needs.
Vaccine formulation research
The effects of stress conditions (such as pH, temperature, freeze-thaw, drying, shearing) on molecular structure (such as secondary and tertiary) and function (such as activity, titer, binding force) were explored by using high-throughput prescription research methods to comprehensively understand the behavior of macromolecules under various stress conditions. Most vaccines are liquid preparations, and if the initial liquid formulation strategy does not meet the requirements of the target product characteristics, it is recommended to develop a freeze-dried product using a suitable freeze-drying process. Oral vaccines are given by the oral route and are suitable for the immune response of the digestive system. The nasal vaccine is administered through the nose in a spray form and is intended for upper respiratory tract immunization. The topical adhesive vaccine in development is a relatively novel form and is expected to be administered locally through the skin with an immune effect similar to that of injection. Nanotechnology is used to deliver mRNA and inactivated vaccines.
Vaccine formulation optimization
In the formulation process optimization, the most important content is excipient optimization. The excipients used in vaccine preparations mainly include various buffers, salts, lyophilized protectants (sugars)/fillers, surfactants, antibacterial preservatives, etc., which are designed to optimize the environment around the protein through excipients to maintain its conformation and colloidal stability, reduce interactions between neighboring protein molecules, and block the interaction between the protein and the container surface. And then improve the stability of biologics.
An agonist of the natural immune system or a carrier selectively present at an antigenic target is added to the formulation of a vaccine formulation, known as a vaccine adjuvant. It has an important impact on the immune effect produced by vaccination, can improve the persistence of antigen, broad spectrum, strong and its inherent immunogenicity, reduce the amount of antigen and/or the number of immunizations required to achieve the efficacy, and its self-toxicity is minimal, and the immune effect is long-lasting. Aluminium hydroxide, aluminium phosphate and alum adjuvants are the most commonly used adjuvants in human vaccines.
Vaccine formulation analysis
Compatibility of vaccine components: Ensure that the various components of the vaccine (such as antigens, adjuvants, co-ingredients) can remain chemically and physically stable after mixing, and will not interfere with each other.
Formulation stability: Evaluate the stability of the vaccine under different storage conditions (temperature, humidity, light) to ensure that the vaccine will not fail during long-term storage and transportation.
Toxicological studies: Acute toxicity tests are typically administered with a single high dose (often several times the lethal dose in animal models) to assess whether a vaccine causes acute adverse effects, including death, organ damage. It is also necessary to evaluate the safety of the vaccine under long-term use and whether it has immunotoxicity.
Immune response testing: Use animal models (usually mice, rabbits, monkeys) to assess whether a vaccine can induce a specific immune response. Serum antibody levels are measured using ELISA, and T cell responses, such as activation of CD4+ and CD8+ T cells, and cytokine secretion, are detected by techniques such as flow cytometry (FACS).
Potency testing: After vaccination, animals are exposed to the corresponding pathogen (such as pathogenic viruses, bacteria) to assess whether the vaccine is effective in protecting the animals from infection or reducing the severity of infection. Evaluate the effects of different doses of vaccine on immune response and protective efficacy to determine the optimal immune dose.
Vaccine formulation manufacturing
BOC Sciences has established a GMP-compliant preparation workshop with advanced equipment and complete functions to provide corresponding drug production and packaging services for clinical trial research. And we also support all steps of protein production including the mutagenesis and cloning of target genes in expression vectors, the heterologous expression in prokaryotic and eukaryotic hosts, as well as the subsequent purification of the corresponding proteins as a service.
FAQ
Our vaccine formulation services cover the entire process from initial vaccine development to commercial production. Including excipients selection, vaccine stability testing, adjuvant selection and optimization, vaccine preparation production process development, and vaccine-related regulations and quality control services.
The choice of vaccine adjuvant depends on the type of vaccine and the target immune response. Adjuvants can enhance the immune response, improve antibody production, or help the immune system better recognize antigens. Commonly used adjuvants include aluminum salt adjuvants, oil-water emulsions, immune stimulants (such as TLR agonists), lipid nanoparticles. We will recommend the appropriate adjuvant for you based on the characteristics of the vaccine, the use scenario and the target immune effect.
Yes, the formulation of a vaccine directly affects its immunogenicity. For example, the concentration of antigens in the vaccine, the type and dosage of adjuvants, the selection of excipients, and the process conditions of the preparation will affect the final immune response. We conduct immunogenicity assessments during vaccine formulation development and optimize formulations based on these assessments.
- Purity and impurity detection
- Immunogenicity test
- Stability test
- Sterility and endotoxin testing
- Bioactivity detection