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Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants
Amanda Jane Leach1, Edward Kim Mulholland2, Mathu Santosham3
1Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia.
Insights
A new vaccine schedule starting at one month of age may offer earlier and broader protection against otitis media (OM) in Indigenous infants. This study compares different pneumococcal conjugate vaccine (PCV) schedules to assess immunogenicity and carriage.
Area of Science:
- Pediatrics
- Immunology
- Infectious Diseases
Background:
- Otitis media (OM) and associated hearing loss significantly impact Indigenous infants in the Northern Territory from early life.
- Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are key pathogens causing OM, colonizing the nasopharynx early.
- Current single vaccine schedules may not provide optimal early protection against these OM pathogens.
Purpose of the Study:
- To evaluate the immunogenicity of different pneumococcal conjugate vaccine (PCV) schedules in infants.
- To compare an investigational early-start vaccine schedule with standard schedules for otitis media prevention.
- To assess the impact of vaccine schedules on nasopharyngeal carriage of key OM pathogens.
Main Methods:
- A randomized, blinded controlled trial involving 425 infants aged 28-38 days.
- Infants were allocated to three PCV schedules: Synflorix (2, 4, 6 months), Prevenar13 (2, 4, 6 months), or an investigational schedule (Synflorix at 1, 2, 4 months + Prevenar13 at 6 months).
- Primary outcomes measured at 7 months included immunogenicity (GMC) and carriage of vaccine-type pneumococci and NTHi; secondary outcomes included OM incidence.
Main Results:
- The study is designed to measure the immunogenicity of specific vaccine antigens, including geometric mean concentration (GMC).
- It will assess the proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi.
- The incidence of otitis media, including tympanic membrane perforations, will be a key secondary outcome.
Conclusions:
- The findings will inform optimal PCV scheduling for early protection against otitis media in high-risk infant populations.
- This research aims to provide evidence for a potentially more effective vaccine strategy to mitigate the long-term effects of OM.
- Results will be disseminated to communities, conferences, and peer-reviewed open-access journals.
Introduction:
Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.
Methods And Analyses:
This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.
Ethics And Dissemination:
Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.
Trial Registration Numbers:
ACTRN12610000544077 and NCT01174849.
