A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda

Author:

Cohen Courtney A1,Balinandi Stephen2,Kuehne Ana I1,Rock Michelle L13,Bonagofski Luke G1,Ricks Keersten M4,Davis Ian4,Abelson Dafna5,Stonier Spencer W1,Odongo Matthew2,Bornholdt Zachary A5,Zeitlin Larry5,Moyer Crystal5,Cose Stephen26ORCID,Dye John M1,Lutwama Julius J2,Herbert Andrew S1ORCID

Affiliation:

1. Virology Division, US Army Medical Research Institute of Infectious Disease , Fort Detrick, Maryland , USA

2. Department of Arbovirology, Medical Research Council/Uganda Viral Research Institute , Entebbe , Uganda

3. The Geneva Foundation , Tacoma, Washington , USA

4. Diagnostic Systems Division, US Army Medical Research Institute of Infectious Disease , Fort Detrick, Maryland , USA

5. Mapp Biopharmaceutical , San Diego, California , USA

6. London School of Hygiene & Tropical Medicine Uganda Research Unit , Entebbe , Uganda

Abstract

Abstract Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%–30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.

Funder

Defense Threat Reduction Agency

Publisher

Oxford University Press (OUP)

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