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Updated: Apr 20, 2026

Assessing Respiratory Immune Responses to Haemophilus Influenzae
Published on: June 29, 2021
Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease
Susan J Pizzutto1, Stephanie T Yerkovich2, John W Upham3
1Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia.
Insights
Vaccination with a protein D conjugate vaccine improved immune responses to non-typeable Haemophilus influenzae (NTHi) in children with chronic lung disease. This conjugate vaccine enhanced cell-mediated and humoral immunity, approaching levels seen in healthy children.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Vaccinology
Background:
- Non-typeable Haemophilus influenzae (NTHi) causes frequent endobronchial infections in children and adults with suppurative airway diseases like bronchiectasis and COPD.
- Patients with these conditions often exhibit impaired cell-mediated immune responses to NTHi, with no current interventions to correct this deficiency.
- This study investigates a potential intervention to improve NTHi-specific immune responses.
Purpose of the Study:
- To determine if vaccination with a conjugate vaccine containing protein D from Haemophilus influenzae is associated with improved NTHi-specific cytokine responses in children suffering from chronic suppurative lung disease.
Main Methods:
- Blood mononuclear cells from 107 children with chronic suppurative lung disease and 32 healthy controls were stimulated in vitro with NTHi.
- Cytokine production was compared between children who received the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and those who received pneumococcal vaccines lacking protein D.
- Protein D-specific IgG1 levels in plasma were quantified.
Main Results:
- Children receiving three or more doses of PHiD-CV produced significantly more IFNγ (interferon-gamma) compared to controls (median 939 vs. 338 pg/ml, p=0.007).
- IFNγ levels in PHiD-CV vaccinated children approached those observed in healthy controls.
- The PHiD-CV was also associated with significant increases in IL-13 (interleukin-13) and IL-5 (interleukin-5) (p<0.001 and p=0.007, respectively).
- Protein D-specific IgG1 levels correlated positively with the number of PHiD-CV doses received (p=0.02).
Conclusions:
- Vaccination with the protein D conjugate vaccine (PHiD-CV) is linked to enhanced NTHi-specific cell-mediated immunity in children with chronic suppurative lung disease.
- PHiD-CV vaccination also demonstrated improvements in NTHi-specific humoral immune responses.
- These findings suggest PHiD-CV may be a valuable intervention for improving immune defense against NTHi in this vulnerable pediatric population.
Background:
Endobronchial infections related to non-typeable Haemophilus influenzae (NTHi) are common in children and adults with suppurative airway disease such as bronchiectasis and COPD. Impaired cell mediated immune responses to NTHi have been described in these patients. Currently there are no interventions known to correct the deficiency in cell mediated immune responses to NTHi. The aim of this study was to determine if receipt of a conjugate vaccine containing protein D from H. influenzae is associated with improvement in NTHi-specific cytokine responses in children with chronic suppurative lung disease.
Methods:
Blood mononuclear cells from 107 young children with chronic suppurative lung disease and 32 healthy control children were stimulated in vitro with NTHi. We compared the cytokine production of stimulated mononuclear cells from children who had received the pneumococcal H. influenzae protein D conjugate vaccine with cells from children who received pneumococcal vaccines without protein D. Protein D-specific IgG1 was quantified in plasma.
Results:
Children with chronic suppurative lung disease who received ≥ 3 doses of the protein D conjugate vaccine produced significantly more IFNγ than children who received the alternative vaccines without protein D (median 939 versus 338 pg/ml; p = 0.007). Importantly, the amount of IFNγ produced by those vaccinated with the conjugate vaccine approached the levels observed in cells from healthy children. The conjugate vaccine was also associated with small but significant increases in IL-13 (p < 0.001) and IL-5 (p = 0.007). Protein D-specific IgG1 levels correlated with the number of PHiD-CV doses (p = 0.02).
Conclusion:
Vaccination with PHiD-CV is associated with improvements in NTHi-specific cell-mediated and humoral immune responses in children with chronic suppurative lung disease.
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