vaccine development process

what is the first step in vaccine development?

< discovery and characterisation of antigens (substances that can induce an immune response)

< need to identify suitable antigens

what does this process include?

< identifying potential antigens: researchers use genomics, proteomics and bioinformatics tools to identify proteins or other molecules from pathogens that can serve as targets for the immune system

< characterising antigens - once potential antigens are identified, they are characterised using various analytical methods such as PCR, western blotting, ELISA and mass spectrometry - these methods help confirm the identity, purity and immunogenic properties of the antigens

common examples include:

< haemagglutinin (HA) of the influenza virus)

< hepatitis B surface antigen of the HBV

< spike S protein of SARS-COV-2

what is the next step?

< after identifying and characterising the antigen, next step is designing the vaccine

< n this stage, researchers choose the appropriate vaccine platform based on the nature of the antigen and the pathogen.

< Different types of vaccines can be developed, including live attenuated, inactivated, subunit, conjugate, DNA, RNA, and vector-based vaccines.

< Computational tools such as bioinformatics and immunoinformatics facilitate the identification of epitopes, helping streamline certain stages of vaccine design while ensuring safety.

< Modern approaches, like structure-based vaccine design, focus on optimizing the surfaces of immunogens to elicit protective antibody responses.

< For instance, in the case of the SARS-CoV-2 spike protein, specific amino acid substitutions, such as proline substitutions at helix-turn-helix motifs, are used to stabilize the prefusion conformation, enhance immunogenicity, and improve vaccine efficacy.

< Additionally, modifications such as domain insertion, deletion, replacement, or combination, like the insertion of oligomeric sequences into the spike protein, can further enhance neutralising antibody responses.

what happens when a vaccine candidate is designed?

< it undergoes rigorous preclinical testing and safety evaluation before being tested in humans.

< Preclinical studies aim to assess safety, immunogenicity, and potential efficacy through in vitro and animal experiments.

< Initial in vitro studies using cultured cells help determine the vaccine's ability to provoke an immune response and identify any cytotoxic effects.

< Subsequently, animal models such as mice, rats, or non-human primates are used to evaluate the vaccine's safety, immunogenicity, and appropriate dosage while identifying potential side effects.

< Toxicology studies are also conducted to evaluate single and repeat-dose toxicity, reproductive toxicity, and other specific safety concerns.

< The data obtained from preclinical testing provide a foundational understanding of how the vaccine might behave in humans and are crucial for advancing to clinical trials.

how are clinical trials conducted?

< in three progressive phases to ensure that the vaccine is safe and effective for human use.

< Phase I trials involve a small group of 20 to 100 healthy volunteers and focus primarily on assessing safety and determining an appropriate dosage, while also providing preliminary data on immune response.

< Phase II trials expand to several hundred participants who reflect the target population and aim to further evaluate safety and immunogenicity, as well as optimize the vaccine dosage and administration schedule.

< Phase III trials involve thousands of participants and are designed to confirm the vaccine’s efficacy and monitor for any rare or serious side effects.

< The results from these large-scale trials form the critical body of evidence required for regulatory evaluation.

what happens are succesfully completing clinical trials?

< vaccine undergoes regulatory review and licensure before it can be widely used. The vaccine manufacturer submits all preclinical and clinical data to regulatory authorities, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

< Regulatory experts thoroughly review the data to ensure the vaccine meets stringent safety, efficacy, and quality standards, including inspections of manufacturing facilities to verify compliance with Good Manufacturing Practices (GMP). If the vaccine meets all requirements, it is granted a licence for public use.

< Even after licensure, post-marketing surveillance, also known as Phase IV, continues to monitor the vaccine's safety and effectiveness in the general population, ensuring that any rare or long-term adverse effects are promptly identified and addressed.

< This meticulous and multi-layered process ensures that vaccines reaching the public are both safe and effective.