Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Gift Chiwala , Raphael Kamng'ona , Evaristar Kudowa , Godwin Tembo , Mphatso Mayuni , Lorensio Chimgoneko , Morrison Kamanga , Faith Thole , Tiyamike Nthandira , Bridgette Galafa , Glory Kadzanja , Tarsizio Chikaonda , John Ndaferankhande , Anthony Chirwa , Edna Nsomba , Lumbani Makhaza , Innocent Sulani , Alfred Muyaya , Neema Toto , Marc Y.R. Henrion , Stephen B. Gordon
{"title":"Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage","authors":"Gift Chiwala ,&nbsp;Raphael Kamng'ona ,&nbsp;Evaristar Kudowa ,&nbsp;Godwin Tembo ,&nbsp;Mphatso Mayuni ,&nbsp;Lorensio Chimgoneko ,&nbsp;Morrison Kamanga ,&nbsp;Faith Thole ,&nbsp;Tiyamike Nthandira ,&nbsp;Bridgette Galafa ,&nbsp;Glory Kadzanja ,&nbsp;Tarsizio Chikaonda ,&nbsp;John Ndaferankhande ,&nbsp;Anthony Chirwa ,&nbsp;Edna Nsomba ,&nbsp;Lumbani Makhaza ,&nbsp;Innocent Sulani ,&nbsp;Alfred Muyaya ,&nbsp;Neema Toto ,&nbsp;Marc Y.R. Henrion ,&nbsp;Stephen B. Gordon","doi":"10.1016/j.clim.2025.110489","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model.</div></div><div><h3>Methods</h3><div>Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of <em>Streptococcus pneumoniae</em> 6B. We categorised the participants into 4 pneumococcal carriage outcome groups - no carriage; natural carriage; experimental carriage; and dual carriage. We then measured neutrophil to lymphocyte ratio (NLR) in nasal mucosa and cytokine levels in nasal lining fluid at 7 days before and 2, 7 and 14 days after inoculation.</div></div><div><h3>Findings</h3><div>We found that 45 % of participants had no carriage, 35 % had natural carriage, 12 % experimental carriage and 8 % dual carriage. At 2- and 7-days post inoculation, all groups showed an increase in NLR compared to 7 days before inoculation, accompanied by small changes in cytokine levels. An early increase in NLR was associated with protection against experimental carriage while cytokines did not associate with carriage pattern.</div></div><div><h3>Conclusion</h3><div>Nasal inoculation with <em>S. pneumoniae</em> 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"276 ","pages":"Article 110489"},"PeriodicalIF":4.5000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661625000646","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model.

Methods

Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of Streptococcus pneumoniae 6B. We categorised the participants into 4 pneumococcal carriage outcome groups - no carriage; natural carriage; experimental carriage; and dual carriage. We then measured neutrophil to lymphocyte ratio (NLR) in nasal mucosa and cytokine levels in nasal lining fluid at 7 days before and 2, 7 and 14 days after inoculation.

Findings

We found that 45 % of participants had no carriage, 35 % had natural carriage, 12 % experimental carriage and 8 % dual carriage. At 2- and 7-days post inoculation, all groups showed an increase in NLR compared to 7 days before inoculation, accompanied by small changes in cytokine levels. An early increase in NLR was associated with protection against experimental carriage while cytokines did not associate with carriage pattern.

Conclusion

Nasal inoculation with S. pneumoniae 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信