November 28, 2024
Two-Dose Pneumococcal Vaccine in Children Demonstrates Non-inferiority to WHO’s Three-dose Schedule in Carriage Prevention - Fewer Child Pneumococcal Shots: New England Journal of Medicine Study Shows Path to Affordable and Sustainable Vaccination Program
Professor Lay-Myint Yoshida and Associate Professor Michiko Toizumi from the Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, in an international collaboration with Professor Kim Mulholland and Professor Stefan Flasche from the London School of Hygiene and Tropical Medicine (LSHTM), UK, and Professor Dang Duc Anh from the National Institute of Hygiene and Epidemiology (NIHE), Vietnam, demonstrated that after catch-up vaccination of pneumococcal conjugate vaccine (PCV) to children under three years of age and 3.5 years after PCV introduction, a two-dose PCV vaccination schedule (one initial vaccination and one booster vaccination: 1p+1) was not inferior to the WHO-recommended three-dose schedule (2p+1 or 3p+0) in controlling vaccine serotype pneumococcus carriage in Vietnamese children.
The results of this study indicate that in a community where VT pneumococci are controlled, the two-dose schedule (1p+1) can be an effective option for preventing pneumococcal carriage and infection in children.
| <Key Points > |
▶Many pneumococcal diseases*1 can be prevented by the pneumococcal conjugate vaccine (PCV)*2, but the high cost of PCV has slowed the introduction of the vaccine in low- and middle-income countries.
▶Several years after the introduction of PCV, herd immunity to vaccine serotype pneumococci was established, resulting in a significant reduction in the circulation of vaccine serotype pneumococci in the community.
▶ Currently, the WHO recommends a three-dose PCV vaccination schedule (2p+1 or 3p+0).*3
It has been hypothesized that once herd immunity against the vaccine serotype pneumococci has been established, a two-dose vaccination schedule (1p+1) may be sufficient to maintain the suppression of vaccine serotype pneumococcus.
▶This study demonstrated that the 1p+1 schedule was non-inferior in efficacy in controlling vaccine serotype pneumococcal carriage compared with the WHO-recommended 3-dose schedule.
▶This research was published in the scientific journal "New England Journal of Medicine" (November 28, 2024, 7:00 a.m. Japan time)
https://www.nejm.org/doi/full/10.1056/NEJMoa2400007.
| <Terminology> |
* 1 Pneumococcal disease
Pneumococcal disease is an infectious disease that can easily become severe, particularly in children under the age of two, and can cause illnesses such as pneumonia, meningitis, bacteremia, sepsis, and otitis media. Globally, it is one of the leading causes of death in children under five, most of which occur in low- and middle-income countries.
* 2 Pneumococcal conjugate vaccine (PCV)
PCV is a vaccine to prevent pneumococcal disease that provides direct (personal immunity to the vaccine recipient) and indirect (herd immunity) protection against pneumococcal serotypes contained in the vaccine (vaccine serotype pneumococci), thereby reducing the carriage of vaccine serotype pneumococci and thus disease occurrence.
* 3 WHO recommended vaccination schedule
The World Health Organization (WHO) recommends administering PCV according to one of the following schedules:
● Primary 3-dose vaccination schedule (3p+0): 3 doses during infancy
● Two doses of primary vaccination + booster vaccination schedule (2p+1): 2 doses in infancy, booster vaccination after 9 months of age
The cost of PCV remains a barrier to its adoption in many low- and middle-income countries.
| < Research Background > |
▶ With the support of Gavi, the Vaccine Alliance (a public-private partnership established in Switzerland in 2000 with the aim of protecting children's lives and people's health by improving vaccination rates in low-income countries), 45 countries around the world had introduced PCV by 2014, and 60 countries (more than 80% of the target countries) by 2019. Because PCV is expensive, the cost of supporting PCV accounts for 40% of Gavi's total budget (Gavi contributed US$3.3 billion to support PCV from 2009 to 2020), and it is important to reduce this cost and increase funding for other important vaccines.
▶ Studies in developed countries have reported that seven years or more after the introduction of PCV, vaccine serotype pneumococci are rarely seen, and there is no difference in efficacy among those receiving four doses and three or fewer doses.
▶ Based on this finding, we hypothesized that if herd immunity against vaccine serotype pneumococci is established, a schedule that reduces the number of PCV vaccinations to two would provide similar preventive effects to the three-dose schedule recommended by the WHO.
| <Research Methods and Results> |
▶ Study location: This study was conducted in Nha Trang, Vietnam, which is one of Nagasaki University's overseas research centers.
▶ Participants: Children living in 27 communes (areas) in Nha Trang City.
▶ Catch-up vaccination: All children under 3 years of age in the PCV intervention group were vaccinated with PCV using the WHO-recommended 3-dose schedule (12,683 children received at least one dose of PCV).
▶ Communes were randomized to one of four PCV vaccination schedules (2p+1, 3p+0, 1p+1, 0p+1), and routine PCV vaccination was introduced one month after catch-up vaccination (31,385 doses were given as a part of routine vaccination). Three communes in the north served as the unvaccinated controls.
▶ Pneumococcal carriage survey: To evaluate the impact of different PCV vaccination schedules on vaccine serotype pneumococcal carriage in children under two years of age in Nha Trang City, carriage surveys were conducted before and annually after PCV introduction (a total of 18,652 children were enrolled across the six surveys). PCR, culture, and microarray assays were used to identify pneumococcus and pneumococcal serotypes.
▶ Non-inferiority analysis: The non-inferiority effect of the 1p+1 schedule compared with the 2p+1 or 3p+0 schedules was analyzed in reducing vaccine serotype pneumococcal carriage.
Figure. Evaluation of PCV Schedules in a Naïve Population in Vietnam |
▶ Results: After approximately 3.5 years of high-coverage use of PCV, the 1p+1 schedule was found to be non-inferior to the 2p+1 or 3p+0 schedules in suppressing the carriage of vaccine serotype pneumococcal carriage in infants. Furthermore, the 0p+1 schedule showed non-inferiority, suggesting its potential use in emergency settings. These results provide useful evidence for future PCV vaccination policies, especially in low- and middle-income countries.
| <Future expectations> |
The study findings suggest that the PCV 1p+1 vaccination schedule could be an alternative to suppress the carriage of vaccine serotype pneumococci. These results are being evaluated by the Vietnamese health authorities and the WHO’s Pneumococcal Working Group for presentation to the WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) who advises on PCV vaccination policies. ,
The potential implementation of a reduced PCV dose schedule will make PCV programs affordable and sustainable. This could reduce Gavi's PCV budget by one-third, freeing up funds for other vital vaccine support to low- and middle-income countries to protect lives and health.
This study was supported by a grant from the Bill & Melinda Gates Foundation (OPP1139859), and the Nagasaki University Nha Trang Cohort Study was supported by a grant from the Japan Agency for Medical Research and Development (AMED) Infectious Disease Research Infrastructure Development Program (JP21wm0125006).
| <Paper information> |
＜Title＞
Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam
<Author>
Lay-Myint Yoshida* , Michiko Toizumi, Hien Anh Thi Nguyen, Billy J. Quilty, Le Thuy Lien, Le Huy Hoang, Chihiro Iwasaki, Mizuki Takegata , Noriko Kitamura, Monica L. Nation, Jason Hinds, Kevin van Zandvoort, Belinda D Ortika, Eileen M. Dunne, Catherine Satzke, Hung Thai Do, Kim Mulholland, Stefan Flasche, and Duc-Anh Dang.
<Magazines> New England Journal of Medicine
<Link> https://www.nejm.org/doi/full/10.1056/NEJMoa2400007
