Related Experiment Video
Updated: Oct 4, 2025
Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Study Protocol for Preventing Early-Onset Pneumonia in Young Children Through Maternal Immunisation: A Multi-Centre
Anne B Chang1,2,3, Maree Toombs1,4, Mark D Chatfield1,4
1Child Health Division and NHMRC Centre for Research Excellence in Paediatric Bronchiectasis (AusBREATHE), Menzies School of Health Research, Charles Darwin University, Casuarina, NT, Australia.
Insights
Maternal vaccination with the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) may reduce acute lower respiratory infections (ALRIs) in infants. This study investigated PHiD-CV
Area of Science:
- Pediatric infectious diseases
- Vaccinology
- Maternal and infant health
Background:
- Acute lower respiratory infections (ALRIs) pose a significant health burden on young children globally.
- Pneumococcal conjugate vaccines (PCV) are effective in reducing paediatric ALRIs, but their impact via maternal immunization is less understood.
- The 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) targets both pneumococcus and H. influenzae, common causes of ALRI.
Purpose of the Study:
- To determine if maternal immunization with PHiD-CV reduces ALRIs in infants during their first year of life.
- To assess the impact of maternal PHiD-CV vaccination on various ALRI definitions.
- To evaluate effects on infant nasopharyngeal carriage, and immune responses to vaccine antigens in a subset of infants.
Main Methods:
- A parallel, multicentre, superiority randomized controlled trial (RCT) with 1:1 allocation in Australia and Malaysia.
- Healthy pregnant women (17-40 years) received a single dose of PHiD-CV or usual care between 27+6 and 34+6 weeks gestation.
- Primary outcome: rate of medically attended ALRIs by 12 months of age. Secondary outcomes included nasopharyngeal carriage and immune responses.
Main Results:
- Data collection and analysis are ongoing; results are pending.
- The study is powered to detect a significant difference in ALRI rates between the PHiD-CV and control groups.
- Microbiological and immunological data will provide insights into vaccine-induced protection mechanisms.
Conclusions:
- Maternal PHiD-CV vaccination holds potential for preventing early-onset ALRIs and preserving infant lung health.
- Findings could inform vaccination strategies to reduce the burden of respiratory infections in vulnerable infants.
- The multicentre design enhances the generalizability of potential findings on PHiD-CV efficacy.
Abstract:
Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.
