A Longitudinal Analysis of Memory Immune Responses in Convalescent Crimean-Congo Hemorrhagic Fever Survivors in Uganda
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.
Authors
- Courtney A. Cohen (ORCID: https://orcid.org/0000-0002-4963-2493)
- Spencer W. Stonier (ORCID: https://orcid.org/0000-0003-4540-3279)
- John M. Dye (ORCID: https://orcid.org/0000-0002-0883-5016)
- Crystal L. Moyer (ORCID: https://orcid.org/0000-0002-0398-6392)
- Stephen Karabyo Balinandi (ORCID: https://orcid.org/0000-0002-3057-0755)
- Larry Zeitlin (ORCID: https://orcid.org/0000-0002-6857-1024)
- Zachary A. Bornholdt (ORCID: https://orcid.org/0000-0002-7557-9219)
- Julius J. Lutwama (ORCID: https://orcid.org/0000-0002-3210-722X)
- Michelle L. Rock
- Dafna M. Abelson (ORCID: https://orcid.org/0000-0003-4627-6902)
- Stephen Cose (ORCID: https://orcid.org/0000-0002-5156-037X)
- Ian Davis (ORCID: https://orcid.org/0000-0002-1566-4972)
- Matthew Odongo (ORCID: https://orcid.org/0000-0001-6530-0117)
- Keersten M. Ricks (ORCID: https://orcid.org/0000-0002-2854-9308)
- Andrew S. Herbert (ORCID: https://orcid.org/0009-0001-5256-7733)
- Luke G. Bonagofski
- Ana I. Kuehne
Institutions
- United States Army Medical Research Institute of Infectious Diseases (US)
- London School of Hygiene & Tropical Medicine (GB)
- Mapp Biopharmaceutical (United States) (US)
- The Geneva Foundation (US)
- Uganda Virus Research Institute (UG)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1093/infdis/jiae395
- Citations
- 6
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- Defense Threat Reduction Agency
- Medical Research Council