Natural Carriage of Streptococcus pneumoniae Is Associated With Increased Experimental Pneumococcal Carriage but Reduced Conjugate Vaccine Efficacy in a Human Challenge Model
Author:
Galafa Bridgette1ORCID, Chikaonda Tarsizio1ORCID, Kudowa Evaristar1, Sichone Simon1ORCID, Sibale Lusako1ORCID, Thole Faith1, Mkandawire Christopher1, Dula Dingase1ORCID, Nsomba Edna1ORCID, Tembo Godwin1ORCID, Chaponda Mphatso1, Chirwa Anthony E1ORCID, Nkhoma Vitumbiko1, Ngoliwa Clara1ORCID, Kamng'ona Raphael1, Toto Neema1ORCID, Makhaza Lumbani1, Muyaya Alfred1, Howard Ashleigh2ORCID, Nyazika Tinashe K2ORCID, Ndaferankhande John1ORCID, Chimgoneko Lorensio1ORCID, Banda Ndaziona P K34ORCID, Chiwala Gift1ORCID, Rylance Jamie1ORCID, Ferreira Daniela25ORCID, Jambo Kondwani C12ORCID, Morton Ben26ORCID, Henrion Marc Y R12ORCID, Gordon Stephen B12ORCID
Affiliation:
1. Malawi Liverpool Wellcome Programme , Blantyre 2. Liverpool School of Tropical Medicine , United Kingdom 3. Department of Medicine, Queen Elizabeth Central Hospital 4. Department of Medicine, Kamuzu University of Health Sciences , Blantyre , Malawi 5. Department of Paediatrics, University of Oxford , Oxford , England 6. Liverpool University Hospitals NHS Foundation Trust , United Kingdom
Abstract
Abstract
Background
In Malawi, the national 13-valent pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than in the United States, 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 serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy.
Methods
Healthy adults aged 18 to 40 years were randomly assigned to 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) colony-forming units/100 µL at 28 days postvaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 postinoculation using culture and multiplex quantitative polymerase chain reaction (qPCR) targeting the lytA/cpsA genes, and we compared carriage rates by vaccination status.
Results
Of 204 participants, 19.6% (n = 40) exhibited experimental carriage detected by culture and 25.5% (n = 52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n = 10/98) than the placebo group (28.3%, 30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13, 8%, 6/75; placebo, 25.9%, 21/81) vs those with natural carriage (PCV13, 14.8%, 4/27; placebo, 26.5%, 9/34). According to a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had lower VE (52%) vs participants with no natural carriage (69%).
Conclusions
We have shown that the PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers when compared with those without natural carriage at the inoculation visit.
Funder
Wellcome Trust Liverpool School of Tropical Medicine
Publisher
Oxford University Press (OUP)
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