In line with our mission to help people live longer, healthier lives, FHI Clinical has teams working on studies worldwide. Many of these projects aim to address preventable infectious diseases such as pneumonia, malaria, Ebola and COVID-19 that continue to be public health issues. Vaccine development is key to eradicating many of these diseases and can make a significant difference in the lives of those affected. We’re proud to say that the results of recent studies that we supported focusing on vaccination against Streptococcus pneumoniae, a Gram-positive bacterium that is responsible for the majority of community-acquired pneumonia, were recently published, providing more evidence for health departments to use when developing their pediatric vaccination strategies.
Epidemiology of Streptococcus pneumoniae
For children younger than five years old, S. pneumoniae (the pneumococcus) causes significant morbidity and mortality, especially in the form of pneumococcal pneumonia for children in low- and middle-income countries (LMIC). In addition, S. pneumoniae can live asymptomatically in the upper respiratory tract, making it easy to unknowingly transmit the disease to others. Children (20-50%) are more likely to be “silent” carriers of S. pneumoniae than adults (5-20%), increasing the importance of preventive strategies in the pediatric population.
Role of vaccination
Because vaccination of children against the common serotypes that cause invasive pneumococcal disease is a key global strategy, the national immunization schedules of 147 countries already include pneumococcal conjugate vaccines (PCVs), which are effective against S. pneumoniae. An additional 18 countries are planning on introducing a PCV into their schedules.
What is a serotype?
Within a single species of microorganisms, such as bacteria or viruses, a serotype is a group that shares distinctive structures on their surfaces.
There are currently two PCVs licensed for pediatric use:
- 10-valent PCV (PCV10; Synflorix ® , GlaxoSmithKline)
- 13-valent PCV (PCV13; Prevenar ®, Pfizer)
They both cover the same 10 serotypes, and Prevenar covers an additional three serotypes. They are most commonly administered in the following dosing schedules: 3+0 (three primary shots and no booster), 2+1 (two primary shots and one booster shot), 3+1 (three primary shots and one booster shot).
Serotypes included in the pneumococcal conjugate vaccines (PCVs) licensed for pediatric use
Serotype | Synflorix® (10-valent) | Prevenar® (13-valent) |
|---|---|---|
1 | ||
3 | – | |
4 | ||
5 | ||
6A | – | |
6B | ||
7F | ||
9V | ||
14 | ||
18C | ||
19A | – | |
19F | ||
23F |
Vietnam pneumococcal project
However, there is limited information available for health agencies to make a decision around which vaccine to use and how many doses to administer. To help address this lack of evidence, the Murdoch Children’s Research Institute (MCRI) undertook Phase II/III studies of available PCVs in collaboration with:
The FHI Clinical team, led by Zen Hafy, supported the studies over the eight-year period by monitoring the three sites and central laboratory in Ho Chi Minh City, Vietnam.
Head-to-head vaccine comparison
In the first study, the team conducted a head-to-head comparison of the immunogenicity (the ability to provoke an immune response) and reactogenicity (the physical signs of the inflammatory response to vaccination) of PCV10 and PCV13 in a parallel, open-label, randomized controlled trial. Healthy infants in Ho Chi Minh City were randomized to one of six PCV schedules (including primary doses + booster):
1. | 3 + 1 PCV10 |
2. | 3 + 0 PCV10 |
3. | 2 + 1 PCV10 |
4. | 2 + 0 PCV10 |
5. | 2 + 1 PCV13 |
6. | Control (no vaccination) |
The study team found that both PCV10 and PCV13 have a strong ability to induce an immune response (are highly immunogenic) and produce a similar physical response (reactogenicity; fever, skin reddening) when used in a 2+1 schedule. Observed differences in immunogenicity varied by serotype and timepoint after vaccination. The study provided additional information about the magnitude of response and allows countries to make a choice about which vaccine to use based on those responses, cost, and the importance of specific serotype within their setting.
Effects of PCV10 versus PCV13 on pneumococcal carriage
Based on these results, the second study aimed to determine if PCV10 and PCV13, both administered in 2+1 schedules, differed in their effect on the levels of S. pneumoniae in the nose and throat in children (up to two years old). In addition, data from the unvaccinated group were used to determine the most commonly circulating serotypes.
As the study team recently reported recently reported in the journal Vaccine, compared with unvaccinated children:
- Children vaccinated with PCV10 had lower levels of the ten S. pneumoniae serotypes (45-62% lower) in their nose and throat.
- Children vaccinated with PCV13 had lower levels of the 13 S. pneumoniae serotypes (36-49% lower) in their nose and throat.
The greatest difference between unvaccinated and vaccinated children was observed when the children were 18 months old.
There were few differences between PCV10 and PCV13 vaccination, although PCV13 did also result in significantly lower levels of the three additional serotypes that it protects against (3, 6A, 19A). Both vaccination groups had a significantly reduced chance of carrying the ten serotypes shared by the two vaccines, when compared with unvaccinated children. The majority of the serotypes present in unvaccinated children were those that are covered by both vaccines (6A, 6B, 14, 19A, 19F, 23F). Therefore, introduction of either vaccine would likely contribute to herd protection and reduce the infection rate in countries using these vaccines.
Collaboration and commitment key to generating quality evidence
“The commitment of the teams at the sites and central laboratory was very high,” Zen said. “It is very impressive that the results from the entire study could be published only a few months after study closure.”
There were few differences between PCV10 and PCV13 vaccination, although PCV13 did also result in significantly lower levels of the three additional serotypes that it protects against (3, 6A, 19A). Both vaccination groups had a significantly reduced chance of carrying the ten serotypes shared by the two vaccines, when compared with unvaccinated children. The majority of the serotypes present in unvaccinated children were those that are covered by both vaccines (6A, 6B, 14, 19A, 19F, 23F). Therefore, introduction of either vaccine would likely contribute to herd protection and reduce the infection rate in countries using these vaccines.
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