CLINICAL TRIALS ON VACCINES

The development and testing of vaccines typically go through several stages of clinical trials before they are approved and launched on the market. These stages are designed to ensure the safety, efficacy, and quality of the vaccine.

Here are the typical stages of clinical trials for vaccines:

1. Preclinical Stage: This stage involves laboratory testing and experimentation with the vaccine candidate using cell cultures and animal models. Researchers assess the vaccine’s safety profile, immune response generation, and potential side effects. If the preclinical results are promising, the vaccine moves on to the next stage.

• In Vitro Studies: Researchers begin by conducting in vitro studies, which involve testing the vaccine candidate in cell cultures. These studies help assess the vaccine’s ability to stimulate an immune response and identify any potential toxic or harmful effects on cells.
• Animal Model Testing: Vaccine candidates are then evaluated in animal models, such as mice, rats, rabbits, or non-human primates. Animal studies help researchers understand the vaccine’s safety and efficacy in living organisms. They also provide insights into dosage levels, potential side effects, and immune response generation.
• Safety Assessment: One of the primary objectives of preclinical trials is to assess the safety of the vaccine candidate. Researchers closely monitor the animals for any signs of adverse reactions or toxic effects resulting from the vaccine administration. This includes evaluating general health, organ function, and potential systemic or local reactions.
• Immunogenicity Evaluation: Another important aspect of preclinical studies is assessing the vaccine’s ability to generate an immune response. Researchers analyze the animal subjects’ immune systems to measure specific antibody production, T-cell response, and other markers of immunogenicity. This data helps determine the vaccine’s potential effectiveness in stimulating an immune response in humans.
• Dose Optimization: Preclinical trials also involve identifying the optimal dosage levels for the vaccine. Different dosages may be tested in animals to determine the most effective dose that achieves the desired immune response without causing significant side effects.
• Toxicity Studies: Researchers conduct detailed toxicity studies to identify any potential toxic effects of the vaccine candidate. This involves evaluating various organs, tissues, and physiological parameters to ensure the vaccine does not cause significant harm.
• Duration of Immunity: Preclinical studies can also provide insights into the duration of vaccine-induced immunity. Researchers track the persistence of immune responses over time to understand how long the vaccine’s protective effects may last.

Regulatory Submission: The data collected during the preclinical stage is compiled and submitted to regulatory authorities as part of the investigational new drug (IND) application. This submission is a prerequisite for moving to the clinical trial phases.

Phase I clinical trials are the initial stage of testing in humans to assess the safety, dosage, and potential side effects of a vaccine candidate. These trials typically involve a small group of healthy volunteers and aim to gather preliminary data on the vaccine’s safety profile and immune response generation.

Here’s a closer look at Phase I clinical trials for vaccine:

• Objectives: The primary objectives of Phase I trials are to evaluate the safety and tolerability of the vaccine candidate in humans. Researchers also assess the vaccine’s ability to provoke an immune response, including the production of specific antibodies or activation of T-cells.
• Study Design: Phase I trials often employ an escalation study design. Initially, a small subgroup of participants receives the lowest expected dose necessary to elicit an immune response. Subsequent subgroups are then administered increased dosing regimens until the maximum tolerable dose is determined. This design helps minimize the chances of serious adverse effects and determines the optimal dosage for subsequent phases.
• Participant Selection: Healthy volunteers are typically recruited for Phase I trials. These individuals may not have the disease the vaccine is targeting but should meet certain eligibility criteria established by the researchers. Eligibility criteria may include age restrictions, general health requirements, and exclusion of participants with underlying medical conditions that could interfere with the trial’s objectives.
• Safety Evaluation: The safety evaluation in Phase I trials is comprehensive. Participants are closely monitored for any adverse events or side effects following vaccination. Researchers collect data on local reactions (e.g., pain, redness, swelling at the injection site) as well as systemic reactions (e.g., fever, fatigue, headache). If any serious adverse events occur, they are thoroughly investigated.
• Immunogenicity Assessment: Phase I trials also assess the vaccine’s ability to elicit an immune response. Researchers analyze participants’ blood samples to measure the production of specific antibodies or activation of T-cells. This data helps determine whether the vaccine is generating the desired immune response and provides insights into potential efficacy.
• Dose Optimization: Alongside safety evaluation, Phase I trials aim to establish the optimal dosage for subsequent phases. By administering different dose levels to participants, researchers can assess the relationship between dosage and immune response. The goal is to find the balance between achieving a robust immune response and minimizing side effects.
• Duration and Follow-up: Phase I trials typically involve a relatively short duration of follow-up. Researchers monitor participants for a certain period after vaccination to observe any delayed side effects or potential waning of immune response over time.
• Ethical Considerations: Phase I trials follow strict ethical guidelines to protect participant rights and safety. Informed consent is obtained from each participant, ensuring they are fully informed about the trial’s procedures, potential risks, and benefits before enrolment.

The data obtained from Phase I trials provides important preliminary information on the vaccines candidate’s safety and immunogenicity. If the vaccine shows promising results and an acceptable safety profile, it can progress to Phase II trials for further evaluation.

2. Phase 2: During this stage, the vaccine is administered to a larger group of several hundred participants, including individuals who have characteristics (e.g., age, health conditions) similar to the target population. Phase 2 trials further assess the vaccine’s safety, immunogenicity (ability to provoke an immune response), optimal dosage, and potential adverse effects. These trials help establish the appropriate dosing regimen for subsequent phases.

3. Phase 3: This is the final stage of testing before regulatory approval. Thousands to tens of thousands of participants are enrolled in Phase 3 trials, representing the target population for the vaccine. These trials provide a more comprehensive assessment of the vaccine’s efficacy, safety, and potential side effects in real-world conditions. Participants are randomly assigned to receive either the experimental vaccines or a placebo, and researchers monitor the occurrence of infections, symptoms, and adverse events. The data collected during this phase is crucial for determining the vaccine’s effectiveness and informing regulatory decisions.

4. Regulatory Review: After completing Phase 3 trials, the vaccines developer submits all the data and findings to regulatory authorities, such as the Food and Drug Administration (FDA) in the United States or the European Medicines Agency (EMA) in Europe. Regulatory agencies evaluate the vaccine’s safety, efficacy, manufacturing processes, and labeling information. If the data is deemed satisfactory, the regulatory authorities may grant approval for the vaccine to be marketed.

5. Phase 4 (Post-Marketing Surveillance): Once the vaccine is approved and launched on the market, Phase 4 trials continue to monitor the vaccine’s safety and effectiveness in larger populations. These trials collect additional long-term data and assess rare side effects that may not have been captured during the earlier phases.

It’s important to note that the specific details and requirements for clinical trials can vary depending on the vaccines, disease being targeted, and regulatory guidelines of different countries or regions.

If you have any inquiries regarding clinical trials on vaccines or if you would like to discuss your upcoming project and how Convex can contribute to its successful execution, please do not hesitate to contact us. You can reach us at info@convex.bg, and we would be delighted to respond to your inquiries and provide you with the necessary information.