How do we develop a first-of-its-kind vaccine?

Developing a vaccine is no easy feat. The process typically takes 10 to 15 years and encompasses multiple complex stages: a research-intensive exploratory phase to identify a promising antigen; preclinical animal studies to establish vaccine candidate viability; human clinical trials to demonstrate safety and efficacy and determine dosage and vaccination schedule; regulatory review and approval; manufacturing and scale-up; quality control, which includes additional postlicensing studies to make sure a vaccine is performing as anticipated; and pharmacovigilance to monitor for any adverse events.

It’s hard enough to navigate this process when building a “me too” vaccine—a new or improved version of a vaccine that's already on the market (like a new diphtheria, tetanus, and pertussis [DTaP] vaccine). Imagine doing it without an exact blueprint and developing a vaccine against a disease for which no licensed vaccine currently exists (a "novel" or "first-of-its-kind" vaccine). Even harder is targeting that vaccine toward the low- and middle-income countries that need it most.

Take Group B Streptococcus (GBS). It’s the leading cause of sepsis and meningitis in young infants worldwide, yet no licensed vaccine currently exists to protect against it. The bacterium, present in the gastrointestinal tract and vagina of 20 percent of women worldwide, causes as many as 3.5 million preterm births and nearly 150,000 stillbirths and infant deaths annually. High-income countries have access to antenatal screening and treatment, but these measures are often impractical and out of reach for the low-resource countries that suffer the highest burden. The world is getting closer to a solution—candidate vaccines have made it to clinical study and added to the knowledge base—but a licensed vaccine is critical to empower mothers and give infants worldwide a healthy start in life.

PATH is supporting the development of just such a vaccine. It will be a challenge, no doubt; there are no instructions for how to build and license a GBS vaccine and we can’t guarantee that any given attempt will be successful. But we’re confident. Because while first-of-its-kind vaccine development is a highly technical, complex process, PATH follows tried-and-true philosophies that ensure we’re set up for success—whether we have a blueprint or not.

Vaccine development doesn’t start in the lab. It starts with passionate, dedicated people and it hinges on partnerships. Partners should have complementary strengths and skills, be committed to nurturing long-term relationships, and most importantly, be working toward the same mission.

We’re collaborating with Seattle-area biotech Inventprise to develop a GBS vaccine. It’s an advantageous pairing—PATH has expertise across the vaccine development spectrum, from discovery to delivery; Inventprise has conjugate vaccine expertise and is exploring new development technologies that could lead to more effective vaccines. None of that would matter, though, if Inventprise—like PATH—didn’t believe in making vaccines affordable and accessible to the countries that need them most.

GBS is a global problem and a vaccine would have market potential worldwide. African nations alone, however, account for 54 percent of all estimated GBS cases and 65 percent of GBS-linked stillbirths and infant deaths—demonstrating the inherent inequity in our current treatment and prevention methods. A vaccine would make little difference toward reducing global GBS morbidity and mortality if it were only available to high-income countries.

Partnership isn’t just about who has the skills to build a product. It’s about who’s willing to work together toward the same outcome. Vaccine development is an expensive endeavor—between $200 million and $500 million on the conservative side—and it often yields an expensive product. For PATH, the right partner is one committed to changing the paradigm.

Vaccine performance hinges on a number of considerations, including life stage, health status, and location. Infants, for instance, have less developed immune systems than do adults and might need multiple doses; the elderly often have weakened immune systems and might require vaccines made more potent by adjuvants. Low-resource countries face further challenges that mean vaccines developed for high-income nations—beyond being unaffordable—sometimes simply aren’t as effective. Disease strain prevalence can differ depending on location, so a vaccine formulated for a high-income market may not be protective in a low-income one. And coinfection with HIV can sometimes affect the body’s immune response to a vaccine, leaving countries with high rates of HIV infection with a less effective product. Moreover, multidose vaccines, which may be routine in countries with strong health systems, can be impractical in places where health care visits are infrequent.

We’re pursuing a single-dose, multivalent GBS vaccine designed for use in low-resource countries and for maternal immunization—the process of vaccinating a woman during pregnancy to protect her child. This means an eventual vaccine could be administered to pregnant mothers in a single health care visit and potentially prevent more than 90 percent of GBS disease in young infants. We’re also using conjugate vaccine technology, which confers long-lasting protection even in disease-endemic settings, and which has been successful against other bacteria like pneumococcus and meningococcus.

Study methods matter, too. Large-scale efficacy studies—which measure the frequency of disease within a vaccinated population and are considered the gold standard for vaccine evaluation—may be an impractical assessment method for a GBS vaccine. A correlates of protection study, on the other hand, which looks for measurable signs of protection (such as a specified level of disease antibodies), may be a more efficient and affordable way to one day bring a GBS vaccine to market. Every vaccine has unique needs and risks and if we can find the best ways to manage and mitigate those, we can find success.

“Me too” vaccines are proven products with established pathways for development and licensure. We know it’s possible to create a DTaP vaccine, for instance, because it’s been done. The development process, the regulatory pathway, the demonstrated efficacy—it all exists. Not so for a novel vaccine, and many attempts fail. In fact, studies estimate the probability of a preclinical candidate vaccine one day entering the market at less than 10 percent. Even more challenging is that while maternal immunization has a safe and effective track record against a number of diseases, no vaccines have yet been licensed with a specific indication for maternal administration, posing additional regulatory and delivery challenges. Novel vaccine development is a process loaded with risk—in product outcome and in financial investment—that not all developers will choose (or have the resources) to pursue.

But it’s not impossible. While we may not have a precise blueprint for how to make a GBS vaccine, there’s a lot we do know. We know how to make conjugate vaccines. We know how to make vaccines that are safe for pregnant women. We know how to license multivalent conjugate vaccines against other bacterial pathogens. We learn from what our partners and colleagues have done in the past, we improve on it, and we make it relatable for GBS. We might not have a map, but we do have bread crumbs—if we’re willing to follow them.

To develop a first-of-its-kind vaccine is to be a trailblazer. It requires courage to fail, and courage to persist. But it’s not hard to find courage in the face of GBS; studies show the bacterium causes more infant deaths than HIV, and more than tetanus, pertussis, and respiratory syncytial virus combined. The risks of developing a novel vaccine might be high, but the risks of doing nothing are much higher.

These are only some of the most basic philosophies of novel vaccine development, but they’re critical starting points. With these concepts in mind we’re confident we can see a GBS vaccine—or any other first-of-its-kind vaccine—succeed.