Dataset Information

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

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.

SUBMITTER: Ugwu C

PROVIDER: S-EPMC9790078 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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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 C Olumade Testimony T Nwakpakpa Ebenezer E Onyia Venatius V Odeh Elizabeth E Duruiheoma Rosemary Ogonna RO Ojide Chiedozie K CK Eke Matthew Afam MA Nwafor Ifeanyi Emmanuel IE Chika-Igwenyi Nneka N Abu Augustine M AM Azuogu Benedict B Ajayi Nnennaya N Ogah Emeka E Ayodeji Oluwafemi O Abejegah Chukwuyem C Adedosu Nelson N Oyejide Nicholas N Abah Sylvester S Omidele Abiola A Ingbian Winifred W Osoba Emmanuel E Eromon Philomena P Oluniyi Paul P Ogunsanya Olusola O Happi Anise A Otuh Patricia P Nadesalingam Angalee A Carnell George G Krause Nina N Aguinam Ernest E Kinsley Rebecca R Storisteanu Daniel Matthew L DML Tonks Paul P Nelson Diana D McAlister Carley C Boisen Matthew M Garry Robert R Wright Edward E Temperton Nigel N Frost Simon S Heeney Jonathan Luke JL Happi Christian C

Scientific reports 20221225 1

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 ...[more]

PMID: 36567369

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Project description:Annual outbreaks of Lassa fever have resulted in a public health threat in Nigeria and other endemic countries in Sub-Saharan Africa. While the Lassa Virus (LASV) is endemic in rodent populations, zoonotic spillover to humans causes annual outbreaks. This study reviewed the burden of Lassa fever (LF) in Nigeria between 2020 and 2023 and conducted a cross-sectional survey of Nigerians to evaluate their risk perceptions of LF. During the period under review, 28,780 suspected and 4,036 confirmed cases of LF were reported from 34 of the 37 states of Nigeria. These cases resulted in 762 deaths (a CFR of 18.9%). The overall case positivity rate was 14% (4,036/28,780), with more positive cases in 2020 (17.5%, n = 1,189/6,791). A total of 2,150 study participants were enrolled in the prospective cross-sectional study, with most of them (87.5%, n = 1,881/2,150) having previously heard of Lassa fever (LF). The numerical scoring system revealed that 35.43% (n = 762/1,881) of those aware of LF have poor knowledge of its preventive measures, route of transmission, and control measures. Approximately 6.84% (n = 147/2,150) of them were at a high risk of contracting LF, with 27.6% (n = 584/2,150) of study participants feeling concerned about contracting LF because of the presence of rodents in their immediate vicinity, occupational exposure to healthcare workers, and the probability of contamination of food by infected rodents without necessary food safety measures. Multivariable logistic regression analysis revealed that tertiary education was associated with an increased likelihood of better LF knowledge (OR: 17.32; 95% CI: 10.62, 28.26; p < 0.01) and a lower risk of contracting LF when compared to respondents with no formal education. In addition, study participants who reside in low-burden states have lower LF perception than those residents in high-LF-burden states (OR: 0.59; 95% CI: 0.38-0.91; p = 0.049). On the other hand, study participants with poor risk perception (knowledge) of LF had a higher likelihood (RR: 0.33; 95% CI: 0.20, 0.53; p < 0.01) of contracting LF when compared to those with good knowledge of LF. Similarly, those residents in low LF burden states were less likely (OR: 0.09; 95% CI: 0.05,0.17; p < 0.01) to contract LF when compared to those residents in high burden states. There is a need to improve LF diagnostics capacity, infection prevention and control measures, and implementation of the One Health approach to controlling LASV from animal reservoirs. In addition, public enlightenment campaigns to address fundamental knowledge gaps are crucial to mitigating the ongoing and future impact of LF in Nigeria.

Project description:BackgroundDefining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.MethodsWe compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination.ResultsWe showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination.ConclusionTogether, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.Trial registrationRegistration is not required for observational studies.FundingThis study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Dataset Information

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

Publications

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

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