Outwitting wily pneumonia bacteria with a new vaccine

Pneumococcal disease is an infection — particularly severe in older people — caused by the bacteria Streptococcus pneumoniae. The infection can manifest in two primary forms: invasive and non-invasive. In the invasive form, the pneumococcal disease spreads beyond the initial infection site to the blood or even to the brain and spinal cord. Non-invasive pneumococcal disease typically stays in the lungs and causes pneumonia. This form of the disease is the most prevalent in adults, with more than 150,000 hospitalizations reported annually in the United States (1).

Paula Annunziato in a grey suit jacket standing with her hands crossed

Paula Annunziato is Merck’s Senior Vice President of Infectious Diseases and Vaccines, leading her team in developing vaccines for pneumococcal diseases.

CREDIT: Merck

“Streptococcus pneumoniae… it's sort of a wily bacteria. I remember a professor of mine actually using that word ‘wily’ to describe it,” said Paula Annunziato, a pediatrician and Senior Vice President of Infectious Diseases and Vaccines Clinical Research at Merck. “[It has] all these ways in which it's able to escape human immunity.”

With her experience overseeing the development of numerous vaccines, including Gardasil for human papillomavirus, Annunziato set her sights on pneumococcal diseases.

She and her team at Merck developed the vaccine CAPVAXIVE which offers adults protection against multiple strains of S. pneumoniae (2). The vaccine, which requires only one dose, was recently approved by the Food and Drug Administration.

What motivated Merck to develop this new vaccine for pneumococcal diseases?

There have been vaccines against invasive pneumococcal diseases for years. Merck, of course, manufactures Pneumovax 23, so we know this area well. But people do not appreciate that sometimes, even when there is an effective vaccine, there are still people who suffer from the disease. It depends on the pathogen diversity and how well the vaccines match that diversity. One way that pathogens escape immune recognition is with their polysaccharide capsule. There are more than 100 different types of polysaccharide capsules. Because of this, none of the existing vaccines can prevent every single type of bacteria in nature. However, as vaccine developers, we try to develop vaccines that are the best match for the disease burden that's out there in the community. We're excited about CAPVAXIVE because, for older adults and those with certain underlying conditions, CAPVAXIVE matches the disease burden best compared to the other available vaccines.

How is CAPVAXIVE different from other pneumococcal vaccines?

We went back to the drawing board in some ways for this vaccine. We looked at the epidemiology of the pneumococcal serotypes causing the disease in the older population, as opposed to the infant and pediatric populations. When we looked at the epidemiology, it was interesting because different serotypes were causing residual disease in these two distinct populations. So, for CAPVAXIVE, if we focused on the disease burden in adults and asked how we could design a vaccine that would address that best. We came up with a complement of 21 serotypes conjugated to a protein, which covered 85 percent of the invasive pneumococcal disease in adults in the United States, according to the most recent survey reports from the CDC. It's a complement to the pediatric vaccines. That’s going to make a huge difference in terms of preventing pneumonia and invasive pneumococcal disease in older people who are still at significant risk of having severe infections. We're really excited about this recent approval.

Streptococcus pneumoniae… it's sort of a wily bacteria.
- Paula Annunziato, Merck

What was your reaction to the positive results from the Phase 3 trials?

As you can imagine, we were really happy. We never know what the results are going to be until the studies are unblinded, which is always a little nerve wracking. When we start a large vaccine program like this, we think we’re going to be successful, but we won’t know until we see the results. We were thrilled when we saw the results of the Phase 3 program.

Did you get any feedback from patients or families on the vaccine?

We spent a lot of time talking to the physicians who enrolled the participants in our trials and the scientific leaders in this area. There was a huge amount of enthusiasm for the overall idea of having a vaccine specifically and uniquely developed for adults. All of the investigators, staff, and participants have been really happy to be part of this positive experience with these results.

What was one of the most exciting part of working on this pipeline?

I'm excited to be part of a company where we thought very carefully and thoroughly about how to make a substantial and important difference in developing the next generation of pneumococcal vaccines. I'm pleased and proud that the company moved away from the paradigm of giving the same vaccine to pediatric patients and adults. Instead, we looked at what each population needs and spent the time and resources researching and developing specific vaccines for each population. This will change the epidemiology of pneumococcal diseases as more people can be protected.

What are some of Merck's long-term goals for other vaccine development pipelines?

Merck is very committed to vaccine development. One of the things about vaccine development is that we are not done when we have the first approval. It's just the beginning of the journey in many ways. We're committed to supporting and bringing CAPVAXIVE to those who need it. In addition, we have several other vaccines in our pipeline and portfolio, as well as other preventions that are not vaccines traditionally but will be used very similarly to vaccines. I'm excited to be in this business.