Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria.
Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria.
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LASSA热幸存者中对LASSA热病毒的体液和细胞免疫反应及其在尼日利亚南部暴露的接触。
DOI：
10.1038/s41598-022-26045-w
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发表时间：
2022-12-25
影响因子：
4.6
通讯作者：
Happi, Christian
中科院分区：
文献类型：
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作者：
Ugwu, Chinedu;Olumade, Testimony;Nwakpakpa, Ebenezer;Onyia, Venatius;Odeh, Elizabeth;Duruiheoma, Rosemary Ogonna;Ojide, Chiedozie K.;Eke, Matthew Afam;Nwafor, Ifeanyi Emmanuel;Chika-Igwenyi, Nneka;Abu, Augustine M.;Azuogu, Benedict;Ajayi, Nnennaya;Ogah, Emeka;Ayodeji, Oluwafemi;Abejegah, Chukwuyem;Adedosu, Nelson;Oyejide, Nicholas;Abah, Sylvester;Omidele, Abiola;Ingbian, Winifred;Osoba, Emmanuel;Eromon, Philomena;Oluniyi, Paul;Ogunsanya, Olusola;Happi, Anise;Otuh, Patricia;Nadesalingam, Angalee;Carnell, George;Krause, Nina;Aguinam, Ernest;Kinsley, Rebecca;Storisteanu, Daniel Matthew L.;Tonks, Paul;Nelson, Diana;McAlister, Carley;Boisen, Matthew;Garry, Robert;Wright, Edward;Temperton, Nigel;Frost, Simon;Heeney, Jonathan Luke;Happi, Christian
阐明自然保护对拉沙热（LF）的适应性免疫特性对设计和选择最佳候选疫苗至关重要。随着人们对拉沙病毒重新产生兴趣，并呼吁加快拉沙病毒疫苗的研究，有必要确定对拉沙病毒的自然保护性免疫反应的相关因素。在这里，我们描述了尼日利亚LASV流行区LF幸存者（N = 370）及其暴露接触者（N = 170）中存在的细胞和抗体免疫反应。有趣的是，我们的数据显示，幸存者及其接触者的T细胞和结合抗体反应相当，而中和抗体反应主要见于LF幸存者，而不是他们的接触者。发现中和抗体反应对所有5个LASV谱系都有交叉反应，对尼日利亚南部流行的谱系II有强烈偏向。我们证明，10年后，LF幸存者的外周血中检测不到T细胞和抗体反应。值得注意的是，LF幸存者在六个月内保持高水平的可检测结合抗体反应，而他们的接触者则没有。最后，作为潜在的疫苗靶点，我们确定了LASV糖蛋白（GP）和核蛋白（NP）诱导最广泛的肽特异性T细胞反应的区域。综上所述，这些数据为评估LASV候选疫苗的临床试验提供了免疫学读数和潜在基准。
Elucidating the adaptive immune characteristics of natural protection to Lassa fever (LF) is vital in designing and selecting optimal vaccine candidates. With rejuvenated interest in LF and a call for accelerated research on the Lassa virus (LASV) vaccine, there is a need to define the correlates of natural protective immune responses to LF. Here, we describe cellular and antibody immune responses present in survivors of LF (N = 370) and their exposed contacts (N = 170) in a LASV endemic region in Nigeria. Interestingly, our data showed comparable T cell and binding antibody responses from both survivors and their contacts, while neutralizing antibody responses were primarily seen in the LF survivors and not their contacts. Neutralizing antibody responses were found to be cross-reactive against all five lineages of LASV with a strong bias to Lineage II, the prevalent strain in southern Nigeria. We demonstrated that both T cell and antibody responses were not detectable in peripheral blood after a decade in LF survivors. Notably LF survivors maintained high levels of detectable binding antibody response for six months while their contacts did not. Lastly, as potential vaccine targets, we identified the regions of the LASV Glycoprotein (GP) and Nucleoprotein (NP) that induced the broadest peptide-specific T cell responses. Taken together this data informs immunological readouts and potential benchmarks for clinical trials evaluating LASV vaccine candidates.
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影响因子：
9.2
作者：
Fischer RJ;Purushotham JN;van Doremalen N;Sebastian S;Meade-White K;Cordova K;Letko M;Jeremiah Matson M;Feldmann F;Haddock E;LaCasse R;Saturday G;Lambe T;Gilbert SC;Munster VJ
通讯作者：
Munster VJ
尼日利亚的感染模式，病例死亡率和LASSA病毒的扩散。
影响因子：
3.7
作者：
Yaro CA;Kogi E;Opara KN;Batiha GE;Baty RS;Albrakati A;Altalbawy FMA;Etuh IU;Oni JP
通讯作者：
Oni JP
影响因子：
3.8
作者：
Mateer EJ;Huang C;Shehu NY;Paessler S
通讯作者：
Paessler S
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
影响因子：
5.4
作者：
ter Meulen, J;Badusche, M;Hoerauf, A
通讯作者：
Hoerauf, A