How Vaccines are Made Safe and Effective

Vaccine development is a rigorous, multi-stage process involving extensive collaboration. Here, we outline the full development pathway — from initial discovery through clinical trials — for our new vaccines in the U.S.. Building on research by the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center and GSK, Sabin is advancing Marburg and Sudan ebolavirus viruses using the cAd3 platform through clinical trial testing with the goal of regulatory approval.  

Stages of vaccine development 

Discovery

During the discovery phase, scientists lay the foundation for all the steps that follow in vaccine development including studying the pathogen, conducting exploratory studies in animals to understand immune response for early vaccine candidates, and evaluating vaccine platforms. Once promising candidates are identified, more extensive animal testing is conducted during the preclinical phase to evaluate safety and efficacy before moving to human trials, which are generally conducted in three phases. 

Phase 1

Once an idea shows promise, scientists determine the best formulation, including any necessary preservatives, stabilizers, or adjuvants. They also develop reliable tests for vaccine performance and submit an Investigational New Drug application to the U.S. Food & Drug Administration (FDA) to conduct their first-in-human clinical trial. In Phase 1, the vaccine is tested in fewer than 100 healthy adults in placebo-controlled trials to confirm safety and immune response. This phase typically takes one to two years. 

Sabin’s progress

Phase 1 and 1B trials for Sabin’s single-dose Marburg and Sudan ebolavirus vaccine candidates were completed between 2019 and 2021. Each vaccine was given to 56 adults at sites in the U.S. and Africa and were found to be safe and immunogenic. 

Phase 2

In Phase 2 trials, testing expands to a larger group of people and is typically done in locations where the disease is prevalent or an outbreak is most likely to gather additional safety and, in certain instances, early effectiveness data. This phase typically involves randomization where some participants receive the vaccine and others get a placebo, which allows scientists to study safety and identify the optimal dose. During this phase, methods for manufacturing, stabilizing, packaging, and testing the vaccine are refined, with a focus on producing consistent results in each batch. While Phase 2 can take as little as two years, completing this phase often takes longer. 

Sabin’s progress

Phase 2 trials for Sabin’s Marburg and Sudan candidates are ongoing in Kenya and Uganda, and initial results are expected in 2025. Each trial has dosed 125 participants across two country-based sites and will evaluate safety and immunogenicity. This is a randomized, placebo-controlled, double-blind study, meaning that neither the trial participants nor the researchers will know whether participants receive a vaccine dose or a placebo dose until after the trial is over, an approach used to help reduce experimental bias. This protocol is considered the gold standard for clinical trials. 

Sabin’s Marburg vaccine is also being used in the Rwanda outbreak that was declared on September 27, 2024. More than 1,700 participants have been dosed in an open-label Phase 2 clinical trial that is expected to yield information on safety and immunogenicity.   

Phase 3

This is typically the final stage before licensing. This phase takes three to four years and involves thousands of participants, with numbers depending on the vaccine’s target population. The study size is calculated to detect statistical differences in safety and efficacy between the experimental and control groups, based on factors like disease frequency and dropout rates. As in Phase 2, most Phase 3 studies are randomized and blinded. 

Although most vaccines evaluate and demonstrate effectiveness in studies in humans, some diseases — such as those caused by Marburg virus or Sudan ebolavirus — are so rare it is not ethical or feasible to conduct human efficacy studies. Sporadic outbreaks, erratic case numbers, and unpredictable transmission patterns make clinical efficacy studies challenging. Instead, efficacy is demonstrated in animals and that data is used to infer protection in humans. Sabin is conducting animal efficacy studies like these with non-human primates in parallel with human trials.  

After completion, it can take a few months to up to two years for the vaccine developer to review the trial data and submit a licensing request. In the U.S., the FDA as the regulatory agency assesses the data before the vaccine reaches the public. Following FDA approval, experts from the Centers for Disease Control and Prevention (CDC) review the data to determine eligibility recommendations.  

By the time a vaccine is available, it has been under study for several years, involving hundreds, if not thousands, of people and costing hundreds of millions of dollars. Many candidates are halted at various stages if deemed unsuitable for financial, safety, or lack of efficacy reasons. 

Safety is paramount, before and after licensure 

Prior to conducting clinical trials, vaccines are tested in animals to assess effectiveness and toxicity. These studies help identify potential safety risks and inform dose, regimen, and administration routes for clinical trials. Typically, clinical trials take a step-wise approach to assess safety, starting with healthy adults and then expanding to vulnerable populations such as older adults, children, and pregnant women.  

Throughout the conduct of clinical trials, safety is carefully monitored, with ongoing communication between researchers and safety and ethical review boards and regulatory agencies. Independent safety boards are set up to monitor mild and serious health issues that participants report following vaccination. These adverse events could be a side effect that is related to the vaccine, or a coincidental event that happened following vaccination.  

Safety of vaccines continues to be monitored after licensure. In the U.S., if there is evidence of a potential safety concern, the FDA and CDC assess the risks and take public health action, including revoking a developer’s product license. 

Manufacturing is another essential part of the process. As trials are ongoing, the vaccine is produced in bulk to ensure each batch meets strict quality and regulatory standards. Most vaccines— including Sabin’s vaccine candidates— are manufactured under Good Manufacturing Practice (GMP) regulations. GMP ensures drug safety by setting strict procedures to prevent contamination, mix-ups, errors, and inconsistencies during production. This helps make sure that the final drug product is safe, effective, and of high quality for patient use. 

Overall, vaccine development is a stringent and painstaking process, one in which safety and effectiveness are constantly assessed. A vaccine is approved for use only if it is proven to be safe and effective. Even after licensure in the U.S., a vaccine’s safety is carefully and continuously scrutinized by the government and developer.