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- Title
Expansion of CD8<sup>+</sup> T cell population in Lassa virus survivors with low T cell precursor frequency reveals durable immune response in most survivors.
- Authors
LaVergne, Stephanie M.; Sakabe, Saori; Momoh, Mambu; Kanneh, Lansana; Bond, Nell; Garry, Robert F.; Grant, Donald S.; de la Torre, Juan Carlos; Oldstone, Michael B. A.; Schieffelin, John S.; Sullivan, Brian M.
- 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+ 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. Results: 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 of21 patients (67%) with undetectable CD8+ T cell response had a measurable Lassa virus specific CD8+ T cell response with the 10-day assay. Discussion: 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. Author summary: Lassa virus is estimated to infect several thousand people yearly in West Africa, resulting in many cases of Lassa fever disease associated with high morbidity and lethality. We found that durable cellular immunity exists in many Lassa fever survivors. Though larger studies are needed, these data could help shape vaccine research with a goal of lasting protection with immunization.
- Subjects
WEST Africa; T cells; MONONUCLEAR leukocytes; CELL populations; LASSA fever; IMMUNE response
- Publication
PLoS Neglected Tropical Diseases, 2022, Vol 16, Issue 11, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0010882