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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial
Vaccine: X, Vol.7, pp.1-14
2021
PMID: 33681756
Abstract
Background
Aboriginal children living in remote communities are at high risk of early and persistent otitis media. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are primary pathogens. Vaccines with potential to prevent early OM have not been evaluated in this population. We compared immunogenicity (ELISA and opsonophagocytic activity) of a combination of Synflorix™ (PHiD-CV10, 10 serotypes and protein D of NTHi) and Prevenar13™ (PCV13, 10 serotypes plus 3, 6A, and 19A), with recommended schedules.
Methods
This open-label superiority trial randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to PCV13 (P) at 2–4-6 months (_PPP), PHiD-CV10 (S) at 2–4-6 months (_SSS), or PHiD-CV10 at 1–2–4 plus PCV13 at −6 months (SSSP). Primary outcomes (blinded) were immunogenicity against PCV13-only serotypes 3, 6A, 19A, and PHiD-CV10-only protein D at 7 months. Secondary outcomes include immunogenicity against all serotypes at 2, 4 and 7 months.
Findings
Between 2011 and 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(1 4 1). An intention to treat approach including all available data was used. The SSSP group had superior immunogenicity against serotypes 3, 6A, and 19A compared to _SSS (OPA GMT ratios 8.1 to 59.5, p < 0.001), and against protein D compared to _PPP (GMC ratio 11.9 (95%CI 9.7 to 14.6)). Immune responses to protein D and 3, 6A, and 19A in SSSP were not significantly lower (i.e. no harm) than either _SSS or _PPP. For ten common serotypes responses at 2, 4 and 7 months were superior for SSSP (following 1-, 2-, and 4- doses) than _SSS and _PPP (following 0-, 1-, and 3- doses). At 4 months, _SSS was superior to _PPP. Reactogenicity and hospitalisations were rare and unrelated to the intervention.
Interpretation
From two months, the 1–2–4–6-month combined schedule (SSSP) was safe and significantly more immunogenic than 2–4–6-month schedules. The earlier responses may be beneficial in high-risk populations.
Details
- Title
- Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial
- Authors
- Amanda Jane Leach (Corresponding Author) - Charles Darwin UniversityEdward Kim Mulholland - The University of MelbourneMathuram Santosham - Johns Hopkins UniversityPaul J. Torzillo - Royal Prince Alfred HospitalPeter B McIntyre - National Centre for Immunisation Research & SurveillanceHeidi C Smith-Vaughan - Charles Darwin UniversityNicole Wilson - Charles Darwin UniversityBeth Arrowsmith - Charles Darwin UniversityJemima Beissbarth - Charles Darwin UniversityMark D Chatfield - Charles Darwin UniversityVictor Oguoma - Charles Darwin UniversityPaul Licciardi - Murdoch Children's Research InstituteSue A Skull - The University of Western AustraliaRoss M Andrews - Charles Darwin UniversityJonathan R Carapetis - The University of Western AustraliaJoseph McDonnellVicki Krause - Northern Territory Health ServicesPeter Stanley Morris - Charles Darwin University
- Publication details
- Vaccine: X, Vol.7, pp.1-14
- Publisher
- Elsevier Ltd
- Date published
- 2021
- DOI
- 10.1016/j.jvacx.2021.100086
- ISSN
- 2590-1362
- PMID
- 33681756
- Copyright note
- (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Grant note
- Financial Markets for Children.
- Organisation Unit
- Thompson Institute
- Language
- English
- Record Identifier
- 991121852002621
- Output Type
- Journal article
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