mRNA Vaccines Development

Background

Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of target for the cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoimmunity. As a leader in pre-clinical vaccine development and production, Creative Biolabs is confident in offering the best development services for mRNA cancer vaccines. We combine the traditional as well as the advanced genetic engineering technologies to efficiently develop highly immunogenic mRNA vaccines addressing your urgent needs.

• Application of mRNA Cancer Vaccines

The most straightforward use of mRNA vaccines in oncologic settings is the immunization of patients with mRNA vaccines encoding tumor-associated antigens (TAAs). The second application of mRNA vaccines is the production of personalized vaccines against various cancers. Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient. One such application is the transfection of patient-derived dendritic cells (DCs) with mRNAs encoding TAAs, which leads to the presentation of TAA-derived peptides on the DCs and activation of antigen-specific T cells in vivo. A second application is the transfection of patient-derived T cells with mRNAs encoding chimeric antigen receptors, which allows the T cells to directly recognize a specific antigen expressed on the tumor.

• mRNA Vaccines Design

• Identification and Selection of Neoantigens
  Cancer mRNA vaccines are designed to express TAAs that stimulate cell-mediated immune responses to clear or inhibit cancer cells. Once the target of choice is identified, the gene is sequenced, synthesized, and cloned into the DNA template plasmid. mRNA is transcribed in vitro, and the vaccine is delivered into the subject. Given its fully synthetic nature, any sequence could be designed in silico, synthesized, delivered as an mRNA vaccine, and tested rapidly in vivo in animal models.
• Choice of mRNA Format
  Currently, two forms of mRNA vaccines have been developed: conventional mRNA encoding the antigen of interest flanked by 5' and 3' UTRs, and self-amplifying mRNA derived from the genome of positive-stranded RNA viruses. A conventional mRNA vaccine carries only the coding sequence of the antigen of interest flanked by regulatory regions. Modified nucleosides and sequence optimization are often used to ensure robust protein expression and immunogenicity. In addition to mRNA modification, increasing adjuvant properties in formulation might also be advantageous for vaccination. Self-amplifying mRNA vaccines are commonly based on the engineered RNA genome of positive-sense single-stranded RNA viruses. The mRNA mimics the replicative features of RNA viruses to increase the duration and magnitude of the expression, as well as subsequent immunogenicity of the encoded antigen.
Fig.1 Schematic representation of mRNA vaccines and mechanism of antigen expression.¹
• mRNA Modification
  Modifications to the 5' m⁷G cap, poly(A) tail, 5' and 3' UTR, and nucleosides are fundamental to optimize the stability and translational efficiency of all in vitro transcription (IVT) mRNA for all RNA vaccines. Arrays of antigen sequences can also be designed and rapidly tested to generate vaccines with efficient leader sequences, optimal codon usage, enhanced neutralization capacity, or reduced undesired cross-reactivity.
• Choice of Delivery Route and Formulation
  The delivery route and formulation of mRNA vaccines are crucial to determine the kinetics and magnitude of antigen expression as well as the potency of the immune response. LNPs are a popular delivery vehicle for self-amplifying mRNA vaccines. Cell penetrating peptides (CPPs) represent promising tools for mRNA delivery into intracellular target sites. Protamine is an arginine-rich cationic peptide that can bind to mRNA and transport it into the cytoplasm.

mRNA Vaccines Services

Creative Biolabs' vaccine development services help reduce the cost of failure and increase the chance of clinical success for researchers and vaccine companies. If you are interested in our mRNA cancer vaccine development services, please feel free to contact us for more information.

Highlights

• Personalized mRNA Vaccine Solutions: We offer tailored mRNA vaccine development services that enable the production of personalized cancer vaccines, designed to target specific tumor-associated antigens (TAAs) for enhanced patient outcomes.
• Innovative Neoantigen Identification: Our mRNA cancer vaccines are designed to express neoantigens derived from tumor-specific mutations, minimizing the risk of autoimmunity and promoting a robust immune response against cancer cells.
• Comprehensive mRNA Vaccine Design: Creative Biolabs provides end-to-end mRNA vaccine design services, from neoantigen identification and mRNA synthesis to vaccine formulation, ensuring a streamlined and efficient development process.
• Self-Amplifying mRNA Technology: We utilize self-amplifying mRNA derived from positive-stranded RNA viruses to enhance the duration and magnitude of antigen expression, improving the immunogenicity and effectiveness of our cancer vaccines.
• Optimized mRNA Modification: Our expertise in mRNA modification ensures increased stability and translational efficiency of the vaccines, with tailored 5' and 3' UTRs, poly(A) tails, and nucleoside modifications to optimize vaccine performance.
• Cost-Effective Vaccine Development: We provide cost-effective mRNA cancer vaccine development services, reducing the risk of failure and increasing the likelihood of clinical success, making us a trusted partner for researchers and vaccine companies.

FAQs

Published Data

The study explored the use of a non-inflammatory mRNA vaccine for treating experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. The vaccine utilized 1-methylpseudouridine (m1Ψ) modified mRNA, designed to encode disease-related autoantigens. The mRNA was delivered systemically and was shown to result in antigen presentation by splenic CD11c+ antigen-presenting cells without inducing inflammatory responses. Experimental results indicated that the mRNA vaccine effectively expanded regulatory T cells (Tregs) that suppress the activity of autoreactive T cells, leading to a reduction in disease symptoms. The treatment successfully prevented disease progression in mice and induced strong bystander immunosuppression, showing potential for treating complex autoimmune diseases by promoting immune tolerance without compromising overall immune function.

Fig.2 Antigen-encoding m1Ψ mRNA treatment alleviates EAE symptoms in mice.²

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References

1. Maruggi, G.; et al. mRNA as a transformative technology for vaccine development to control infectious diseases. Molecular Therapy. 2019, 27(4): 757-772.
2. Krienke, Christina, et al. "A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis." Science 371.6525 (2021): 145-153.