PneuMatters Study: Preventing early-onset pneumonia in children through maternal immunisation: a multi-centre randomised control trial (RCT)
- National Health and Medical Research Council (NHMRC)
- Menzies School of Health Research
- Queensland University of Technology
- University of Adelaide
- The University of Queensland
- Royal Prince Alfred Hospital
- Griffith University
- Duke University, USA
- Likas Children’s Hospital, Kota Kinabalu, Malaysia
- Logan Hospital
- Toowoomba Hospital
- Royal Brisbane and Women’s Hospital
- Royal Darwin Hospital
- To compare the incidence of any medically attended ALRI in the first 12 months of life by maternal receipt of the 10vPHiD-CV at 27(+6 days) – 34(+6 days) weeks of gestation.
- Evaluate the impact of maternal vaccination with 10v PHiD-CV on nasopharyngeal carriage of Hi and vaccine-type Spn serotypes at birth, 6 and 12 months of age.
- Evaluate the potential of maternal vaccination with PHiD-CV to improve cell-mediated (cytokine) and humoral (saliva and serum antibody) immune responses to Spn, non-typeable H. influenzae (NTHi) and Protein D in the mother and infant from birth (birth, 6 and 12 months of age).
- Evaluate the potential of maternal vaccination with PHiD-CV to improve breastmilk antibody immune responses to Spn, non-typeable H. influenzae (NTHi) and Protein D in the mother at birth and at 3, 6, and 12 months postpartum.
- Evaluate the safety of PHiD-CV vaccine in pregnancy. Safety assessments will include local and systemic reactions post-vaccination and serious adverse events up to the infant turning 12 months of age as per GCP criteria.
- Evaluate reasons why Indigenous pregnant women accept/refuse vaccinations.
- Evaluate the role of the gut microbiome in pregnant women and their infants and its role in respiratory infections in infants.
- Investigate host gene biomarkers for ALRI in pregnant women and their infants.
Maternal immunisation for the most common cause of bacterial ALRI in children, Streptococcus pneumoniae (Spn), is not routine but Australian guidelines recommend using a single dose of either the 13valent pneumococcal conjugate vaccine (PCV) or 23-valent polysaccharide vaccine (PPV23) for those with an increased risk of invasive Spn disease. However, 8 RCTs using PPV23 in the 3rd trimester have shown no benefit. The newer PCVs are more immunogenic and effective than the 3-decade old PPV23 but the sole maternal immunisation RCT using a PCV (unlicensed 9valent PCV [9vPCV]) found suppressed immune responses and increased ear disease in the infants at 6-months of age. This may have resulted from interference by high maternally transferred antibodies causing vaccine-induced hyporesponsiveness following in-utero exposure to the vaccine antigens or the conjugating protein used in the 9vPCV and other PCVs. A 10valent PCV (10vPHiD-CV) conjugates most of the antigens to different proteins; thus, potentially limits the hyporesponsiveness effect. Further, 10vPHiD-CV offers some protection against Haemophilus influenzae (Hi - a well-recognised lung pathogen) but has not been studied for maternal immunisation.
Our pilot work showed that children who were 10vPHiD-CV immunised as infants (compared to other PCVs) had improved systemic immunity to Hi and reduced lower airway infection risk (odds ratio (OR) 0.46, 95% confidence interval 0.24-0.88). Further, our pilot data showed hyporesponsiveness to 10vPHiD-CV did not occur in infants of mothers who had PPV23.
Implications for policy and practice:
Maternal immunisation with 10vPHiD-CV has considerable promise for preventing ALRIs in infants at high risk of ALRI.
For further information about the study, email Cate Wilson.
The project commenced in 2018 and will be completed in 2022.