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

Article scientifique 2022 Anglais

Résumé

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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Ugwu, C., Olumade, T., Nwakpakpa, E., Onyia, V., Odeh, E., Duruiheoma, R. O., Ojide, C. K., Eke, M. A., Nwafor, I. E., Chika-Igwenyi, N. M., Abu, A., Azuogu, B. N., Ajayi, N. A., Ogah, E. O., Ayodeji, O., Abejegah, C., Adedosu, N., Oyejide, N., Abah, S., Omidele, A. A., Ingbian, W., Osoba, E., Eromon, P., Oluniyi, P. E., Ogunsanya, O., Happi, A. N., Otuh, P., Nadesalingam, A., Carnell, G., Krause, N., Aguinam, E. T., Kinsley, R., Storisteanu, D. M. L., Tonks, P., Nelson, D. S., McAlister, C., Boisen, M. L., Garry, R. F., Wright, E., Temperton, N., Frost, S. D. W., Heeney, J. L., & Happi, C. (2022). Humoral and cellular immune responses to Lassa fever virus in Lassa fever survivors and their exposed contacts in Southern Nigeria. Scientific Reports. https://doi.org/10.1038/s41598-022-26045-w

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Auteur(s)

Chinedu Ugwu Testimony Olumade Ebenezer Nwakpakpa Venatius Onyia Elizabeth Odeh Rosemary Ogonna Duruiheoma Chiedozie Kingsley Ojide Matthew Afam Eke Ifeanyi Emmanuel Nwafor Nneka Marian Chika-Igwenyi Augustine Abu Benedict Ndubueze Azuogu Nnennaya Anthony Ajayi Emeka Onwe Ogah Oluwafemi Ayodeji Chukwuyem Abejegah Nelson Adedosu Nicholas Oyejide Sylvester Abah Abiola A. Omidele Winifred Ingbian Emmanuel Osoba Philomena Eromon Paul E. Oluniyi Olusola Ogunsanya Anise N. Happi Patricia Otuh Angalee Nadesalingam George Carnell Nina Krause Ernest T. Aguinam Rebecca Kinsley Daniel M. L. Storisteanu Paul Tonks Diana S. Nelson Carley McAlister Matthew L. Boisen Robert F. Garry Edward Wright Nigel Temperton Simon D. W. Frost Jonathan L. Heeney Christian Happi

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