Vaccine Therapy: Development Stages & it's Challenges!

An overview of development stages of vaccine therapies and challenges encountered by the researchers and development scientists along the way. 

What is a vaccine therapy?

A vaccine therapy utilizes modified version of a virus or a bacteria to stimulate the immune system to fight a disease. Vaccine therapies are given after a diagnosis or to prevent recurrence or relapse, while preventive vaccines are given before exposure to a pathogen. Vaccine therapies can treat infectious diseases, like HIV or hepatitis C, or non-infectious diseases, like cancer or autoimmune disorders.

What are the steps of vaccine therapy development?

These are the 10 main stages of vaccine therapy creation and the difficulties that researchers encounter at each stage, from basic research to clinical trials and regulatory approval.

· Stage 1: Selection of the Disease and the Antigen. The first step is to select the disease that the vaccine therapy will treat and the antigen that will trigger the immune response. The antigen can be a whole or a part of a virus or bacteria, or a molecule that is linked to the disease. The challenge is to find an antigen that is specific, safe, and effective for the disease.

·  Stage 2: Selection of Vaccine Type and the Administration Route. Stage 2 is to decide on the Vaccine type and its route of administration. The vaccine type can be a weakened or killed virus or bacteria, a virus or bacteria carrier, a DNA or RNA vaccine, a protein or peptide vaccine, or a cell-based vaccine. The administration route can be an injection, a nasal spray, a patch, or an oral form. The core challenge than is to select a type and a route that are suitable, stable, and scalable.

· Stage 3: Evaluate the Vaccine in Pre-Clinical models. The third stage is to assess the safety and effectiveness of the vaccine in animals, such as mice, rats, rabbits, or monkeys. The preclinical models help to measure the immune response, the prevention against the disease, the best dose and timing, and the possible side effects of the vaccine. The difficulty is to find a model that is suitable and representative for the human disease and response.

· Stage 4: Make the vaccine for human trials. The fourth stage is to make enough vaccine with enough quality for testing on humans. The vaccine development has several steps, like fermenting, purifying, mixing, filling, and packaging. The challenge is to make sure that the vaccine is safe, pure, strong, and consistent.

· Step 5: Phase I clinical trials. The fifth stage is to evaluate the safety and immunogenicity of the vaccine in a small group of healthy volunteers or patients with the specific disease. The phase I trials help to establish the safety profile, the most frequent adverse reactions, the best dose and schedule, and the immune response of the vaccine. The challenge is to attract and keep participants, track and report adverse events, and assess the immunological outcomes.

·  Step 6: Phase II clinical trials. This step is to see how well and safely the vaccine works in a bigger group of patients who have the disease. The phase II trials check the clinical benefit, the disease prevention, the immune response duration, and the safety and comfort of the vaccine. The hard part is to plan and execute a fair, controlled, and blind trial, to assess the core endpoints, KPIs and reference standards, etc. and to understand the statistical and clinical meaning of the results.

·  Step 7: Phase III clinical trials. The seventh stage is to evaluate the effectiveness and safety of the vaccine in a very large group of people with the target disease. The phase III trials help to verify the clinical benefit, the immunity against the disease, the long-term safety and effectiveness, and the cost-benefit of the vaccine. The challenge is to recruit and monitor a sufficient number of participants, to ensure the quality and reliability of the data, and to compare the vaccine with the best available standard of care.

· Step 8: Apply for Regulatory Approval. The final step is to ask the regulators, like the FDA in the US or the EMA in the EU, to approve the vaccine. The approval process requires submitting a file of data and evidence from the lab and human tests, and the production and quality control details. The challenge is to follow the regulatory rules and criteria, to deal with the feedback from the reviewers, and to get the approval quickly.

·  Step 9: Produce and Distribute the Vaccine. The final step is to make the vaccine in bulk and send it to the market. The vaccine distribution process has several steps, such as storing, transporting, delivering, and administering the vaccine. The challenge is to maintain the supply chain, the cold chain, the inventory management, and the availability and affordability of the vaccine.

·  Step 10: Follow up on the Vaccine in Post-Marketing Surveillance. The last step is to continually assess the safety and effectiveness of the vaccine in the real-world situation. The post-marketing surveillance helps to find and report any rare or serious side effects, to assess the long-term results and impact, and to spot any emerging resistance or escape variants. The challenge is to gather and analyze the data from different sources, such as registries, databases, surveys, or studies, and to share the findings and recommendations with the public and the health authorities. 

References

- Plotkin, S., Robinson, J. M., Cunningham, G., Iqbal, R., & Larsen, S. (2017). The complexity and cost of vaccine manufacturing–An overview. Vaccine, 35(33), 4064-4071.

- Hugle, T., & Chatelain, R. (2013). Regulatory pathways for the development of vaccines. In Vaccine analysis: strategies, principles, and control (pp. 223-248). Springer, Berlin, Heidelberg.

- World Health Organization. (2019). Vaccine safety basics e-learning course.

- Law, P. C., & Jackwood, M. W. (2019). A review of basic principles for animal vaccine development. Veterinary microbiology, 239, 108415.

- Kinch, M. S., & Koleski, J. (2020). An overview of FDA-approved vaccines & their innovators. Expert review of vaccines, 19(11), 1033-1045.