在人类攻毒模型中，肺炎链球菌的自然携带与实验性肺炎球菌携带增加相关，但与结合疫苗效力降低相关。

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

作者信息

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 K, Ndaferankhande John, Chimgoneko Lorensio, Banda Ndaziona P K, Chiwala Gift, Rylance Jamie, Ferreira Daniela, Jambo Kondwani C, Morton Ben, Henrion Marc Y R, Gordon Stephen B

机构信息

Malawi Liverpool Wellcome Programme, Blantyre.

Liverpool School of Tropical Medicine, United Kingdom.

出版信息

J Infect Dis. 2025 Feb 20;231(2):334-343. doi: 10.1093/infdis/jiae341.

DOI:10.1093/infdis/jiae341

PMID:38984706

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841637/

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.

摘要

背景

在马拉维，13价肺炎球菌结合疫苗（PCV13）显示出的群体免疫效果低于美国，这可能是由于肺炎球菌自然携带率较高。我们评估了PCV13对健康马拉维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型外的任何血清型肺炎球菌携带）如何影响实验性携带率和疫苗效力。

方法

将18至40岁的健康成年人随机分为PCV13组（n = 98）或生理盐水组（n = 106），然后在接种疫苗后28天，分别以20000（n = 40）、80000（n = 74）或160000（n = 90）菌落形成单位/100μL的剂量进行6B型肺炎链球菌鼻内接种。我们在接种后第2、7和14天使用针对lytA/cpsA基因的培养和多重定量聚合酶链反应（qPCR）评估接种前后的自然和实验性肺炎球菌携带情况，并比较不同疫苗接种状态下的携带率。

结果

在204名参与者中，19.6%（n = 40）通过培养检测出有实验性携带，25.5%（n = 52）通过qPCR检测出有实验性携带。接种疫苗的个体实验性携带率（10.2%，n = 10/98）低于安慰剂组（28.3%，30/106）。在没有自然携带史的参与者中（PCV13组，8%，6/75；安慰剂组，25.9%，21/81），与有自然携带史的参与者（PCV13组，14.8%，4/27；安慰剂组，26.5%，9/34）相比，这种疫苗效力差异更为明显。根据对数二项模型，无论通过培养还是qPCR评估，疫苗效力（VE）均为62%。有自然携带史的参与者的疫苗效力（52%）低于无自然携带史的参与者（69%）。