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Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model

Galafa, Bridgette, Chikaonda, Tarsizio, Kudowa, Evaristar, Sichone, Simon, Sibale, Lusako, Thole, Faith, Mkandawire, Christopher, Dula, Dingase, Nsomba, Edna, Tembo, Godwin, Chaponda, Mphatso, Chirwa, Anthony E, Nkhoma, Vitumbiko, Ngoliwa, Clara, Kamng'ona, Raphael, Toto, Neema, Makhaza, Lumbani, Muyaya, Alfred, Howard, Ashleigh, Nyazika, Tinashe, Ndaferankhande, John, Chimgoneko, Lorensio, Banda, Ndaziona P K, Chiwala, Gift, Rylance, Jamie, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Henrion, Marc and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2024) 'Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model'. Journal of Infectious Disease. (In Press)

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Abstract

Background
In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy.
Methods
Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status.
Results
Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%).
Conclusion
We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit.

Item Type: Article
Additional Information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Subjects: WC Communicable Diseases > WC 20 Research (General)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Repository link:
Item titleItem URI
Dataset for 'Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model'https://archive.lstmed.ac.uk/25105/
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/infdis/jiae341
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 08 Aug 2024 14:37
Last Modified: 10 Oct 2024 13:13
URI: https://archive.lstmed.ac.uk/id/eprint/24957

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