Why Do Vaccines Take So Long to Develop? 

“It takes ten years or more to bring a vaccine from concept to public use for a number of reasons,” explains Jason Maguire, Vice President of Clinical Development for Sabin’s Research and Development team.  

First, researchers must understand the basic science, including immune system function as it relates to the disease they hope to target. “It requires knowing immune system responses to viruses versus parasites versus bacteria, what the best target is for that disease at the cellular level for the vaccine, and also what will be the best platform to deliver the vaccine so that you get a good, sustainable, durable immune response that provides long-term protection against the disease,” Maguire says. 

Researchers must also consider different vaccine delivery methods — injections, oral drops, nasal sprays, infusion — to determine what will best deliver the vaccine to trigger a robust immune response.  

Establishing Safety and Immunogenicity in the Lab and Animal Models Before Clinical Trials 

Preclinical studies are required by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA), to safely move a vaccine “candidate” (a vaccine not yet approved) from the laboratory to clinical trials in humans. They include: 

• Immunogenicity studies to determine the ability of a vaccine candidate to elicit a desired immune response in a laboratory testing, which can occur in a petri dish (using human cells), in a computer model (to determine probabilities), in animal models or in human clinical trials. Study results can help researchers determine which candidates are most promising and even point toward optimal vaccine doses and vaccination schedules. 

• Toxicity and Deelopmental and Reproductive Toxicology studies to assess safety in pre-designated animal models, ensuring no alarming reactions arise that would suggest the vaccine could be harmful. 

• Biodistribution studies to assess how a vaccine distributes throughout the body and how quickly it’s cleared from blood and tissues. These studies are not required for all vaccines, but only for certain types, especially viral vector vaccines and RNA/mRNA vaccines, where regulators need to understand where the vector, RNA, or expressed antigen travels in the body. Traditional protein-based or inactivated vaccines generally do not require standalone biodistribution studies. 

• Efficacy studies to test whether the vaccine candidate can protect against the infection and disease in question.  

Some of these studies may be able to be done concurrently with clinical trials, but it can take two to six years to complete pre-clinical safety trials.  

Beyond Safety to Efficacy 

“Establishing safety in pre-clinical models and early, small in-human studies is a first step, but safety assessments continue to be a critical part of all phases of development,” Maguire says. “If a vaccine does not have an acceptable safety profile, it cannot move forward, regardless of how immunogenic it is. Once you’ve determined safety, then you can move on to efficacy, which is establishing the ability of the vaccine to affect the desired change. A vaccine’s time to licensure is dependent on the disease of interest and how long it’s going to take to establish efficacy.”  

It’s easier to design an efficacy trial for diseases that affect many people, such as COVID-19. The reason: it’s easier to assess whether a vaccine prevents high-incidence disease in placebo-controlled trials where true differences in incidence of disease of interest can be attributed to vaccine. This contrasts to vaccine studies in infrequently occurring (low incidence) diseases; when a disease only appears sporadically, it is harder to prospectively monitor for efficacy. 

Deadly diseases can take even longer to prove efficacy, as clinical challenge trials that involve exposing humans to the disease are considered unethical when exposure can lead to death. In an outbreak clinical trial, placebo doses that offer no protection are also ethically challenging.  

The Stepping Stones of Clinical Trials 

Clinical trials are conducted in three linear “phases.”  

• Phase 1 trials are smaller, generally with fewer than 100 participants, and can help understand both safety in humans and immunogenicity. This phase can last two years or more. 

• Phase 2 trials include slightly larger participant groups, usually with some getting the vaccine candidate and some receiving a placebo (known as a “double blind” study, because researchers do not know who received the vaccine and who did not). This phase also establishes methods for manufacturing, stabilizing, packaging, and testing the vaccine, 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.   

• Phase 3 trials can take three to four years, with one to two more years for analyzing the data from the studies. Trials at this level involve thousands of participants and cost millions of dollars.  

Thinking Outside the Box 

Though none of these steps can be compromised, developing vaccines could be streamlined while remaining just as safe. During the COVID-19 pandemic, Maguire says, we learned that some things can be done differently. 

“It’s basically sped up by multitasking,” he says. “By incorporating things that we used to do in a linear fashion and doing it more concomitantly.” This could mean incorporating certain studies into late-stage trials instead of doing them separately and bringing pediatric studies into earlier phases so that understanding how to serve that population with the vaccine comes earlier.  

Ultimately, “Any process must clearly establish the vaccine’s safety and efficacy,” he says. “This is crucial to maintaining our trust in one of the most important tools we have for fighting disease.” 

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