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 135 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 135 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 135 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.Chest. 2016 Nov;150(5):1101-1108. (PMID: 27400908); Chest. 2010 Jul;138(1):158-64. (PMID: 20173055); Postgrad Med. 2016 Jun;128(5):449-50. (PMID: 27149001); Expert Rev Respir Med. 2012 Aug;6(4):451-65. (PMID: 22971069); Drug Saf. 2015 Nov;38(11):1059-74. (PMID: 26446142); N Engl J Med. 2002 Aug 15;347(7):465-71. (PMID: 12181400); Int J Antimicrob Agents. 2012 Oct;40(4):365-9. (PMID: 22819151); Trials. 2013 Sep 05;14:282. (PMID: 24010917); Clin Exp Immunol. 2008 Jun;152(3):542-51. (PMID: 18462210); Clin Infect Dis. 2008 Mar 1;46(5):726-31. (PMID: 18230042); PLoS One. 2015 Jun 12;10(6):e0129517. (PMID: 26066058); Vaccine. 2000 Dec 8;19 Suppl 1:S108-15. (PMID: 11163473); Vaccine. 2015 Jan 3;33(2):321-6. (PMID: 25448103); Eur Respir J. 2017 Aug 24;50(2):. (PMID: 28838975); Expert Rev Vaccines. 2017 Feb;16(2):109-121. (PMID: 26954689); Pediatr Pulmonol. 2008 Jun;43(6):519-31. (PMID: 18435475); Pediatr Pulmonol. 2012 Jan;47(1):68-75. (PMID: 21830316); Lancet Respir Med. 2013 Oct;1(8):610-620. (PMID: 24461664); Intern Med J. 2016 Jun;46(6):684-93. (PMID: 27009822); PLoS One. 2013 Aug 05;8(8):e70478. (PMID: 23940582); FEMS Immunol Med Microbiol. 2012 Aug;65(3):439-47. (PMID: 22463053); Eur J Clin Microbiol Infect Dis. 2015 Nov;34(11):2275-85. (PMID: 26363637); Chest. 2012 Apr;141(4):1018-1024. (PMID: 21885727); Pediatr Pulmonol. 2016 May;51(5):450-69. (PMID: 26840008); Ann N Y Acad Sci. 2007 Mar;1098:288-311. (PMID: 17435136); Lancet. 2006 Mar 4;367(9512):740-8. (PMID: 16517274); Front Pediatr. 2017 Mar 24;5:58. (PMID: 28393062); Eur Respir J. 1998 Feb;11(2):462-6. (PMID: 9551755); Vaccine. 2017 Feb 1;35(5):747-756. (PMID: 28062125). Linking ISSN: 21645515. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2018 Jul 12. Current Imprints: Publication: 2015- : Philadelphia, PA : Taylor & Francis; Original Imprints: Publication: Austin, Tex. : Landes Bioscience <br />