Role of human Pegivirus infections in whole; Plasmodium falciparum; sporozoite vaccination and controlled human malaria infection in African volunteers

Tumbo, A. M. and Schindler, T. and Dangy, J. P. and Orlova-Fink, N. and Bieri, J. R. and Mpina, M. and Milando, F. A. and Juma, O. and Hamad, A. and Nyakarungu, E. and Chemba, M. and Mtoro, A. and Ramadhan, K. and Olotu, A. and Makweba, D. and Mgaya, S. and Stuart, K. and Perreau, M. and Stapleton, J. T. and Jongo, S. and Hoffman, S. L. and Tanner, M. and Abdulla, S. and Daubenberger, C.. (2021) Role of human Pegivirus infections in whole; Plasmodium falciparum; sporozoite vaccination and controlled human malaria infection in African volunteers. Virol J, 18 (1). p. 28.

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BACKGROUND: Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI). METHODS: HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI. RESULTS: The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5' UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI. CONCLUSIONS: HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Tumbo, Anneth and Schindler, Tobias and Dangy, Jean-Pierre and Orlova-Fink, Nina and Mpina, Maximillian and Tanner, Marcel and Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1743-422X (Electronic)1743-422X (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Dec 2022 10:44
Deposited On:21 Dec 2022 10:44

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