Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms

Patricia Ferrer, Andrea A. Berry, Allison N. Bucsan, Surendra K. Prajapati, Karthik Krishnan, Michelle C. Barbeau, David M. Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F. Billingsley, Faith Pa’ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A. Deye, B. Kim Lee Sim, Stephen L. Hoffman, Kim C. Williamson () and Kirsten E. Lyke ()
Additional contact information
Patricia Ferrer: Uniformed Services University of the Health Sciences
Andrea A. Berry: University of Maryland School of Medicine
Allison N. Bucsan: Uniformed Services University of the Health Sciences
Surendra K. Prajapati: Uniformed Services University of the Health Sciences
Karthik Krishnan: Uniformed Services University of the Health Sciences
Michelle C. Barbeau: Uniformed Services University of the Health Sciences
David M. Rickert: Uniformed Services University of the Health Sciences
Sandra Mendoza Guerrero: Uniformed Services University of the Health Sciences
Miho Usui: Uniformed Services University of the Health Sciences
Yonas Abebe: Sanaria Inc.
Asha Patil: Sanaria Inc.
Sumana Chakravarty: Sanaria Inc.
Peter F. Billingsley: Sanaria Inc.
Faith Pa’ahana-Brown: University of Maryland School of Medicine
Kathy Strauss: University of Maryland School of Medicine
Biraj Shrestha: University of Maryland School of Medicine
Effie Nomicos: Parasitology and International Programs Branch, NIAID, NIH
Gregory A. Deye: Parasitology and International Programs Branch, NIAID, NIH
B. Kim Lee Sim: Sanaria Inc.
Stephen L. Hoffman: Sanaria Inc.
Kim C. Williamson: Uniformed Services University of the Health Sciences
Kirsten E. Lyke: University of Maryland School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants’ second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49041-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49041-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49041-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().