“Rather than simply focusing on the number of serotypes, it is preferable to look at how well the vaccine covers the prevalent serotypes, has good immunogenicity, and is safe.”

Diseases caused by pneumococci are broadly divided into non-invasive pneumococcal disease (NIPD) and invasive pneumococcal disease (IPD), which includes pneumonia, meningitis, and bacteremia.

Currently, all children aged two months to five years and those at high risk of pneumococcal infection, up to 12 years of age, can receive the pneumococcal vaccine free of charge as part of the National Immunization Program (NIP).

There are two types of pneumococcal vaccines included in the Korean NIP: the 13-valent vaccine (PCV13, Prevenar) and the 15-valent vaccine (PCV15, Vaxneuvance), which was introduced last year. In addition, the 20-valent vaccine (PCV20, Prevenar 20) is also on the verge of being introduced to the NIP.

Korea Biomedical Review interviewed Professor Eun Byung-wook of the Department of Pediatrics at Nowon Eulji Medical Center about the selection criteria for pediatric pneumococcal vaccines in clinical practice and the preventive effectiveness of PCV15.

Question: What is the epidemiology of pediatric pneumococcal disease in clinical practice?

Answer: The incidence of pneumococcal disease is highest in infants within the first year of life, and severe infections are also concentrated in this period. This is due to the immature immune system of infants in the first year of life. Acute otitis media and mild pneumonia are non-invasive pneumococcal diseases, while bacteremia, sepsis, severe pneumonia with bacteremia, and meningitis are invasive pneumococcal diseases. Most of these invasive diseases occur in the first 12 months of life.

Ten to 20 years ago, invasive pneumococcal infections were common. However, since the introduction of protein-conjugate vaccines (PCVs), the incidence in children has decreased significantly. However, not all serotypes are covered by the vaccine, so the peak in the first year of life remains. With good coverage of pneumococcal vaccination with NIP, only 20 to 30 severe cases are reported annually.

The introduction of PCV10 and PCV13 into the NIP in 2014 further reduced the incidence of pneumococcal disease. With the recent introduction of PCV15 and other vaccines, the current incidence remains significantly lower than in the past.

Q: Despite the introduction of pneumococcal vaccines into the NIP, infections are still occurring despite high immunization coverage. Why?

A: That’s because infections are caused by serotypes not included in the vaccine. This phenomenon is called serotype replacement. Serotypes included in vaccines can cause infections, but as vaccination rates have increased in recent years, these serotypes have tended to decline, and non-vaccine serotypes have taken their place. The shift is a natural dynamic that occurs as vaccination becomes more widespread. It may lead to a relative decline in the overall preventive effectiveness of vaccines over time.

Q: What are the serotypes of the recent pneumococcal epidemic in Korea?

A: According to surveillance data from the Korea Disease Control and Prevention Agency (KDCA), 65.5 percent of the serotypes that caused pediatric pneumococcal disease in Korea were identified as serotypes not included in existing vaccines, based on data from 2018 to 2019. In particular, serotypes 23A (14.3 percent) and 6C (13.1 percent) accounted for a high proportion, while serotypes included in PCV13 accounted for only 4.8 percent of the total.

These results show that serotype substitution is occurring in Korea due to the introduction of new vaccines. The difference may be even greater if we consider how serotypes tend to change after the pandemic.

Serotypes, such as 23A, 6C, and 10A, have recently emerged as necessary, suggesting the need to develop new vaccines that go beyond the coverage of existing vaccines. Continued surveillance of prevalent serotypes in the country and analysis of trends in these variants will be crucial for developing effective prevention strategies in the future.

Q: PCV15 is the addition of serotypes 3, 22F, and 33F to the existing vaccine. Why is the prevention of these serotypes important from the aspect of immunogenicity?

A: In the pediatric population, the new serotypes 3, 22F, and 33F in PCV15 are serotypes that have been relatively unimportant in the past. Initially, these serotypes were recognized as primarily responsible for causing invasive pneumococcal infections in adults.

However, if these serotypes repeatedly cause infections in adult populations, the strains could be transmitted to children, raising concern about adult-to-pediatric cross-transmission. In this regard, the 15-valent vaccine, including 3, 22F, and 33F, is expected to prevent transmission to children by blocking the major serotypes that occur in adults.

In particular, recent international studies have shown that PCV15 has the potential to inhibit cross-transmission from adults to children. Immunogenicity data are also being reported positively.

Therefore, the 15-valent vaccine represents a meaningful strategic expansion in terms of actual epidemic modification and route of transmission interruption, rather than simply including more serotypes. As additional clinical and epidemiologic data accumulate, our understanding of the importance of these serotypes and the actual effectiveness of the vaccine will deepen.

Q: PCV15 has been introduced in the NIP for more than a year. There is real-world data (RWD) evaluating its clinical efficacy in the country or abroad.

A: A recent report analyzed the effectiveness of switching from PCV13 to PCV15 in some regions of Spain after one year. The data showed that the incidence of serotype three was reduced by about 63 percent, and the overall incidence of IPD was reduced by more than 35 percent.

These results represent significant real-world evidence that the strength of PCV15, which has shown promising clinical outcomes against immune-evading serotype 3, is translating into disease prevention in real-world settings.

However, the results are still limited and should be interpreted with caution, as additional long-term follow-up results over the next three to five years are needed to confirm the persistence of these effects. As PCV15 has only recently been introduced in Korea, research is ongoing.

Q: For some parents, there may be a misconception that the more vaccines there are, the better. What are your thoughts on this, and what are the most critical considerations for vaccine selection in practice?

A: At the end of the day, the key is to have a certain level of immunogenicity. A large number of serotypes does not necessarily mean high immunogenicity. From this perspective, both PCV13 and PCV15, which are used now in Korea, are vaccines that meet specific standards. The most crucial criterion is which serotype is prevalent in the country and how effectively the vaccine can induce an immune response against that serotype.

Q: Pneumococcal vaccines are included in the NIP and are highly effective in preventing pneumonia. However, what unmet medical needs do you see in your practice that need to be addressed?

A: To date, pneumococcal vaccines have not been fully effective in preventing pneumonia, which is why the progression from PCV13 to PCV15 to PCV20 has been an effort to expand coverage to include more serotypes. This direction is expected to continue in the future, and research is underway not only to increase serotype coverage but also to develop vaccines with better immunogenicity.

If better vaccines are developed in the future, policy decisions will need to be made to ensure that they are introduced into the National Immunization Program (NIP) in Korea in a timely and effective manner. The most important basis for this is real-world data. A national data platform should be established to track vaccine effectiveness, adverse events, serotype changes, and other relevant data over the long term, enabling evidence-based policy making and rapid response.

Immunization of high-risk groups is vital. Although they are included in the NIP and therefore have no cost burden, the reality is that they are often not immunized. For example, children with multiple conditions may miss vaccinations because they are focused on treatment, and children in wheelchairs or bedridden may not have the opportunity to get vaccinated because they are unable to visit a doctor. To reduce these immunization blind spots, institutional support such as door-to-door vaccination is needed, along with careful management by healthcare providers.

There is also a need to strengthen educational content for caregivers. Developing videos, card news, and social media content that convey key information, such as serotype changes, family transmission potential, and the importance of vaccination intervals, in an easy-to-understand manner would be effective. Continuous medical education (CME) for healthcare providers and infectious disease prevention education for childcare center teachers should also be organized.