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Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria

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, and others. (2022) Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria. Scientific Reports, 12 . Article Number 22330. E-ISSN 2045-2322. (doi:10.1038/s41598-022-26045-w) (KAR id:99403)

Abstract

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.

Item Type: Article
DOI/Identification number: 10.1038/s41598-022-26045-w
Projects: Project Ovel, ACE-IMPACT
Additional information: For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Uncontrolled keywords: immunology, microbiology, Lassa fever
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Department for International Development (https://ror.org/05rf29967)
Department for International Development (https://ror.org/05rf29967)
Wellcome Trust (https://ror.org/029chgv08)
Depositing User: Nigel Temperton
Date Deposited: 04 Jan 2023 17:16 UTC
Last Modified: 20 Nov 2023 15:39 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/99403 (The current URI for this page, for reference purposes)

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