The clinical, immunological and microbiological impact of the 10-valent pneumococcal-Protein D conjugate vaccine in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: A multi-centre, double-blind, randomised controlled trial

Abstract

We aimed to determine the efficacy of the 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to <18-years with recurrent protracted bacterial bronchitis (rPBB), chronic suppurative lung disease (CSLD) or bronchiectasis. In a multi-centre, double-blind randomised controlled trial, children received two doses, 2-months apart of the 10vPHiD-CV or quadrivalent meningococcal-ACYW conjugate vaccine. Active surveillance for acute exacerbations, respiratory symptoms and antibiotic use was undertaken through to 12-months after the second vaccine dose (clinical cohort only). Serum, saliva and nasopharyngeal swabs were collected to measure immunological and microbiological effects (immunology cohort). Between December 2012 and August 2015, 62 children were enrolled onto the clinical protocol (1 excluded from clinical analyses due to unblinding), while 74 contributed to the immunology cohort (overall mean age = 6.8-years (standard deviation = 3.7), 42 (56.8%) male). The absolute risk difference comparing the 10vPHiD-CV group (n = 31 children) to the MenACYW group (n = 30 children) for acute exacerbations was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0, 0.9). Compared to the MenACYW group, children who received the 10vPHiD-CV were less likely to have respiratory symptoms in each fortnight of surveillance (incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and required fewer short-course (<14-days duration) antibiotics (IDR 0.81, 95% CI 0.61, 1.09). The vaccine was immunogenic and no serious adverse events related to the vaccine were reported. In conclusion, 10vPHiD-CV might have a future role in managing children with rPBB, CSLD and bronchiectasis, but larger multicentre trials are needed to confirm or refute findings from this preliminary study.

Paediatric and adult bronchiectasis: Vaccination in prevention and management

“…To date, there has only been one RCT of PHiD‐CV in either children or adults with bronchiectasis . A small Australian RCT of the vaccine in 61 children with bronchiectasis, CSLD or recurrent protracted bacterial bronchitis did not identify a reduction in any exacerbations; however, it suggested a trend towards a reduction in short (<14 days) antibiotic courses (incidence density ratio (IDR): 0.81; 95% CI: 0.61–1.09) and respiratory symptoms (IDR: 0.82; 95% CI: 0.61–1.10) and there were fewer hospitalised exacerbations in the PHiD‐CV group compared to controls (incidence rate ratio (IRR): 0.16; 95% CI: 0.01–1.02). The vaccine was immunogenic and no related serious adverse events occurred.…”

“…A comparative study in adults with moderate to severe COPD found that PCV‐7 induced greater serotype‐specific functional antibody levels in the serum than PPV‐23, but it lacked sufficient power to determine whether this higher level of immunogenicity translated into fewer exacerbation episodes . A trial of a 10‐valent pneumococcal‐ H. influenzae PD conjugate vaccine (PHiD‐CV) in children with chronic suppurative lung diseases (CSLD, described in the Haemophilus influenzae section) demonstrated robust serum antibody responses to the vaccine‐type pneumococcal serotypes and an indication of some clinical benefit was observed (discussed further in Haemophilus influenzae section). However, the data in that trial were not analysed specifically for children with bronchiectasis.…”

Update on protracted bacterial bronchitis in children

“…Therefore, 2 weeks of Amo treatment was considered to be reasonable, however, further investigations (such as comorbidities, bronchoscopy, culture of BALF, and patients' compliance) should be undertaken and the duration of treatment should be extended if symptoms persisted or relapsed [29,30]. The vaccine may benefit to the management of PBB for it can decrease the respiratory symptoms and antibiotics course [31].…”

Advancing the knowledge, understanding and management of respiratory exacerbations of bronchiectasis in children

“…263 A RCT comparing 10-valent pneumococcal-H.influenzae protein D conjugate vaccine (10vPHiD-CV) to meningococcal-ACWY conjugate vaccine in children (MenACWY) with recurrent PBB, CSLD and bronchiectasis did not achieve its planned sample size. 264 The researchers found that the absolute risk difference comparing the 10vPHiD-CV group (n = 31 children) to the MenACWY group (n = 30 children) for acute exacerbations was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0, 0.9). Compared to the MenACWY group, children who received the 10vPHiD-CV were less likely to have respiratory symptoms in each fortnight of surveillance (incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and…”

“…required fewer short-course (<14-days duration) antibiotics (IDR 0.81, 95%CI 0.61, 1.09). 264 Nevertheless, reports of this vaccine being able to augment the impaired NTHi-specific cell-mediated immunity in children with bronchiectasis are interesting. 265 Although highly desirable, safe and effective candidate vaccines for M. catarrhalis, P. aeruginosa, S. aureus, RSV and HRV are not yet available and are likely to take many years before they become available for adults and children with bronchiectasis.…”