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Dula, Dingase, Morton, Ben 
ORCID: https://orcid.org/0000-0002-6164-2854, Chikaonda, Tarsizio, Chirwa, Anthony, Nsomba, Edna, Nkhoma, Vitumbiko, Ngoliwa, Clara, Sichone, Simon, Galafa, Bridgette, Tembo, Godwin, Chaponda, Mphatso, TotoMtunthama, Neema, Kamng'ona, Raphael, Makhaza, Lumbani, Muyaya, Alfred, Thole, Faith, Kudowa, Evaristar, Howard, Ashleigh, Kenny-Nyazika, Tinashe, Ndaferankhande, John, Mkandawire, Christopher, Chiwala, Gift, Chimgoneko, Lorensio, Banda, Ndaziona, Rylance, Jamie, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Henrion, Marc and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116
(2023)
'Effect of 13-valent pneumococcal conjugate vaccine on
experimental carriage of Streptococcus pneumoniae
serotype 6B in Blantyre, Malawi: a randomised controlled
trial and controlled human infection study'. Lancet Microbe, Vol 4, Issue 9, e683-e691.
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Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi- a randomised controlled trial and controlled human infection study.pdf Available under License Creative Commons Attribution. Download (495kB) | Preview |
Abstract
Background
The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage.
Methods
We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18–40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed.
Findings
Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7–80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci.
Interpretation
This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination.
| Item Type: | Article |
|---|---|
| Subjects: | QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine. WA Public Health > Preventive Medicine > WA 115 Immunization |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW) |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/S2666-5247(23)00178-7 |
| Depositing User: | Christy Littlejohn |
| Date Deposited: | 04 Sep 2023 15:05 |
| Last Modified: | 04 Sep 2023 15:05 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/23067 |
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