Expansion of CD8+ T cell population in Lassa virus survivors with low T cell precursor frequency reveals durable immune response in most survivors.

• Main Authors: Stephanie M LaVergne (Author), Saori Sakabe (Author), Mambu Momoh (Author), Lansana Kanneh (Author), Nell Bond (Author), Robert F Garry (Author), Donald S Grant (Author), Juan Carlos de la Torre (Author), Michael B A Oldstone (Author), John S Schieffelin (Author), Brian M Sullivan (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<h4>Introduction</h4>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.<h4>Methods</h4>We investigated Lassa virus specific CD8+ 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+ T cell response underwent further analysis using a 10-day T cell proliferation assays to evaluate for low T cell precursor frequency.<h4>Results</h4>Forty-five of the 93 LF survivors did not have a Lassa virus specific CD8+ 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+ 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+ T cell response had a measurable Lassa virus specific CD8+ T cell response with the 10-day assay.<h4>Discussion</h4>Despite reports of strong CD8+ T cell responses during acute Lassa virus infection, circulating Lassa virus-specific CD8+ 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+ 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.

Item Description

1935-2727
1935-2735
10.1371/journal.pntd.0010882