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Role of human Pegivirus infections in whole; Plasmodium falciparum; sporozoite vaccination and controlled human malaria infection in African volunteers
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4646064
Author(s)
Tumbo, A. M.; Schindler, T.; Dangy, J. P.; Orlova-Fink, N.; Bieri, J. R.; Mpina, M.; Milando, F. A.; Juma, O.; Hamad, A.; Nyakarungu, E.; Chemba, M.; Mtoro, A.; Ramadhan, K.; Olotu, A.; Makweba, D.; Mgaya, S.; Stuart, K.; Perreau, M.; Stapleton, J. T.; Jongo, S.; Hoffman, S. L.; Tanner, M.; Abdulla, S.; Daubenberger, C.
Role of human Pegivirus infections in whole; Plasmodium falciparum; sporozoite vaccination and controlled human malaria infection in African volunteers
Journal
Virol J
Volume
18
Number
1
Pages / Article-Number
28
Keywords
Antibody response; Controlled human malaria infection; Human pegivirus; Immune activation; Malaria; PfSPZ vaccine
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.
