Natural Carriage of Streptococcus pneumoniae Is Associated With Increased Experimental Pneumococcal Carriage but Reduced Conjugate Vaccine Efficacy in a Human Challenge Model.

IF 5 2区医学 Q2 IMMUNOLOGY

Journal of Infectious Diseases Pub Date : 2025-02-20 DOI:10.1093/infdis/jiae341

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 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.

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在人类挑战模型中，肺炎链球菌的自然携带与实验性肺炎球菌携带的增加有关，但却降低了结合疫苗的效力。

背景：在马拉维，国家肺炎球菌结合疫苗（PCV13）的群体免疫力低于美国，这可能是由于天然肺炎球菌携带率较高。我们评估了 PCV13 对马拉维健康成年人实验性肺炎球菌携带的有效性。我们探讨了自然携带（除 6B 以外的任何其他血清型的肺炎球菌携带）对实验性携带率和疫苗效力的影响。方法：18-40 岁的健康成年人被随机分配接种 PCV13（n=98）或生理盐水（n=106），然后在接种后 28 天进行 SPN 6B 鼻内接种，接种量为 20,000（n=40）、80,000（n=74）或 160,000（n=90）CFU/100µl。我们使用培养和针对 lytA/cpsA 基因的多重 qPCR 技术评估了接种疫苗前后第 2、7 和 14 天的自然和实验性肺炎球菌携带情况，并比较了不同接种情况下的携带率：在 204 名参与者中，19.6%（40 人）表现出实验性携带，通过培养检测到，25.5%（52 人）通过 qPCR 检测到。与安慰剂组（28.3%，n=30/106）相比，接种疫苗者的实验性携带率较低（10.2%，n=10/98）。与有自然携带者（PCV13=14.8%，n=4/27 vs. 安慰剂=26.5%，n=9/34）相比，无自然携带者（PCV13=8%，n=6/75 vs. 安慰剂=25.9%，n=21/81）的疫苗效力差异更为明显。使用对数二项式模型，无论是通过培养还是 qPCR 评估，疫苗有效率 (VE) 均为 62%。与没有自然携带的参与者（VE=69%）相比，自然携带者的 VE 较低，为 52%：我们的研究表明，无论是通过培养还是 qPCR 评估携带情况，PCV13 的 VE 估计值（62%）都是可靠的。PCV13 在自然携带者中的 VE 值低于接种时没有自然携带者的 VE 值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infectious Diseases 医学-传染病学

CiteScore

13.50

自引率

3.10%

发文量

449

审稿时长

2-4 weeks

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.