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Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review

Lucinde, RK; Ong'ayo, G; Houlihan, C; Bottomley, C; Goldblatt, D; Scott, JAG; Gallagher, KE; (2021) Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review. Vaccine , 39 (36) pp. 5095-5105. 10.1016/j.vaccine.2021.07.033. Green open access

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Abstract

Background: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. Methods: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. Results: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. Conclusion: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose–response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.

Type: Article
Title: Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.vaccine.2021.07.033
Publisher version: http://dx.doi.org/10.1016/j.vaccine.2021.07.033
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Research & Experimental Medicine, Pneumococcal conjugate vaccines, Dose-range, Systematic review, Immunogenicity, ANTIBODY-RESPONSE, SEROLOGICAL CRITERIA, VARYING DOSAGES, IMMUNOGENICITY, POLYSACCHARIDE, SAFETY, TETANUS, INFANTS, DIPHTHERIA, CHILDREN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10134242
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