The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol.

Autor:	Morton B; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.; Critical Care Medicine, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi., Jambo K; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Chikaonda T; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi., Rylance J; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi., Henrion MYR; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Banda NP; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi.; College of Medicine, Malawi, Blantyre, Malawi., Nsomba E; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi., Gondwe J; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi., Ferreira D; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Gordon SB; Lung Health, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.; Department of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi.
Jazyk:	angličtina
Zdroj:	Wellcome open research [Wellcome Open Res] 2022 Jun 16; Vol. 6, pp. 240. Date of Electronic Publication: 2022 Jun 16 (Print Publication: 2021).
DOI:	10.12688/wellcomeopenres.17172.2
Abstrakt:	Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation.  For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113). Competing Interests: No competing interests were disclosed. (Copyright: © 2022 Morton B et al.)
Databáze:	MEDLINE
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