High crossreactivity of human T cell responses between Lassa virus lineages.

Luis Branco, Michael B A Oldstone, John S Schieffelin, Donald S Grant, Robert F Garry, Kristian G Andersen, Pardis C Sabeti, Juan Carlos de la Torre, Christian Happi, Peter O Okokhere, Sylvanus Okogbenin, Onikepe Folarin, Ephraim Ogbaini-Emovon, Ikponmwosa Odia, Philomena Eromon, Brian M Sullivan, Karthik Gangavarapu, Refugio Robles-Sikisaka, Dylan Kotliar, Brian C Ware, Selma D Garcia, Beatrice Cubitt, Lansana Kanneh, John Demby Sandi, Mambu Momoh, Augustine Goba, Nhi Ngo, Jessica N Hartnett, Saori Sakabe

Journal: PLoS pathogens 2020;16(3):e1008352

PMID: 32142546

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Abstract

Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.

Address: Viral-Immunobiology Laboratory, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.; Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone.; Ministry of Health and Sanitation, Freetown, Sierra Leone.; Eastern Polytechnic Institute, Kenema, Sierra Leone.; Njala University, Moyamba, Sierra Leone.; FAS Center for Systems Biology, Harvard University, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.; Scripps Translational Research Institute, The Scripps Research Institute, La Jolla, California, United States of America.; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America.; Zalgen Labs, Germantown, Maryland, United States of America.; African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemers University, Ede, Nigeria.; Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria.; Department of Biological Sciences, Redeemers University, Ede, Nigeria.; Department of Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria.; Department of Medicine, Faculty of Clinical Sciences, Ambrose Alli University, Ekpoma, Nigeria.; College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.; Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.

DOI: 10.1371/journal.ppat.1008352

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MeSH Terms: Africa, Western, Antigens, Viral, CD8-Positive T-Lymphocytes, Cross Reactions, Epitopes, T-Lymphocyte, Female, Humans, Lassa virus, Male, Species Specificity