학술논문

Expansion of CD8.sup.+ T cell population in Lassa virus survivors with low T cell precursor frequency reveals durable immune response in most survivors
Document Type
Report
Source
PLoS Neglected Tropical Diseases. November 28, 2022, Vol. 16 Issue 11, pe0010882
Subject
United States
Language
English
ISSN
1935-2727
Abstract
Introduction Lassa virus is a priority pathogen for vaccine research and development, however the duration of cellular immunity and protection in Lassa fever (LF) survivors remains unclear. Methods We investigated Lassa virus specific CD8.sup.+ T cell responses in 93 LF survivors. Peripheral blood mononuclear cells from these individuals were infected with recombinant vesicular stomatitis virus encoding Lassa virus antigens and virus specific T cell responses were measured after 18-hour incubation. Participants who had undetectable CD8.sup.+ T cell response underwent further analysis using a 10-day T cell proliferation assays to evaluate for low T cell precursor frequency. Results Forty-five of the 93 LF survivors did not have a Lassa virus specific CD8.sup.+ T cell response. Of those with responses and a known date of onset of LF (N = 11), 9 had LF within the last ten years. Most participants without a measurable CD8.sup.+ T cell response were more than 10 years removed from a clinical history of LF (N = 14/16). Fourteen of 21 patients (67%) with undetectable CD8.sup.+ T cell response had a measurable Lassa virus specific CD8.sup.+ T cell response with the 10-day assay. Discussion Despite reports of strong CD8.sup.+ T cell responses during acute Lassa virus infection, circulating Lassa virus-specific CD8.sup.+ T cells declined to undetectable levels in most Lassa fever survivors after ten years when evaluated with an 18-hour T cell stimulation. However, when Lassa virus-specific T cells were expanded prior to restimulation, a Lassa virus-specific CD8.sup.+ T cell response could be detected in many if the samples that were negative in the 18-hour stimulation assay, suggesting that prolonged cellular immunity does exist in Lassa fever survivors at low frequencies.
Author(s): Stephanie M. LaVergne 1,2,*, Saori Sakabe 1, Mambu Momoh 3,4,5, Lansana Kanneh 3,4, Nell Bond 6, Robert F. Garry 6, Donald S. Grant 3,4,7, Juan Carlos de la Torre [...]