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Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients.

ABSTRACT: ABSTRACT Haemorrhagic fever with renal syndrome (HFRS) following Hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses elicited during HTNV infections are considered important, however, this process remains poorly understood. Herein, we have investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor (BCR) repertoire in an HFRS cohort. The serological proﬁles were characterized by a lowered expression level of nucleoprotein (NP)-speciﬁc antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset and moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed a dramatic increase in the immunoglobulin gene diversity which was more significantly progressed in moderate infections. In severe cases, B-cell-related transcription was lower with inflammatory sets overactivated. Taken together, these data suggest the clinical signs and disease recovery in HFRS patients were positively impacted by rapid and efficacious humoral responses.

SUBMITTER: Li Y

PROVIDER: S-EPMC8284976 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients.

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