Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model.
Bridgette Galafa, Tarsizio Chikaonda, Evaristar Kudowa, Simon Sichone, Lusako Sibale, Faith Thole, Christopher Mkandawire, Dingase Dula, Edna Nsomba, Godwin Tembo, Mphatso Chaponda, Anthony E Chirwa, Vitumbiko Nkhoma, Clara Ngoliwa, Raphael Kamng'ona, Neema Toto, Lumbani Makhaza, Alfred Muyaya, Ashleigh Howard, Tinashe K Nyazika, John Ndaferankhande, Lorensio Chimgoneko, Ndaziona P K Banda, Gift Chiwala, Jamie Rylance, Daniela Ferreira, Kondwani C Jambo, Ben Morton, Marc Y R Henrion, Stephen B Gordon
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引用次数: 0
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.
期刊介绍:
Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.