Oneko, M. and Steinhardt, L. C. and Yego, R. and Wiegand, R. E. and Swanson, P. A. and Kc, N. and Akach, D. and Sang, T. and Gutman, J. R. and Nzuu, E. L. and Dungani, A. and Kim Lee Sim, B. and Oloo, P. N. and Otieno, K. and Bii, D. K. and Billingsley, P. F. and James, E. R. and Kariuki, S. and Samuels, A. M. and Jongo, S. and Chebore, W. and Abdulla, S. and Daubenberger, C. and Mpina, M. and Styers, D. and Potter, G. E. and Abarbanell, G. and Richie, T. L. and Hoffman, S. L. and Seder, R. A..
(2021)
Safety, immunogenicity and efficacy of PfSPZ vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial.
Nat Med, 27 (9).
pp. 1636-1645.
Full text not available from this repository.
Official URL: https://edoc.unibas.ch/89325/
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Abstract
The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naive adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 x 10(5), 9.0 x 10(5) or 1.8 x 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 x 10(5) dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vdelta2(+)Vgamma9(+) T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vdelta2(+)Vgamma9(+) T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.
Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Clinical Immunology (Daubenberger) |
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UniBasel Contributors: | Daubenberger, Claudia |
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Item Type: | Article, refereed |
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Article Subtype: | Research Article |
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ISSN: | 1546-170X (Electronic)1078-8956 (Linking) |
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Note: | Publication type according to Uni Basel Research Database: Journal article |
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Identification Number: | |
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Last Modified: | 21 Dec 2022 09:14 |
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Deposited On: | 21 Dec 2022 09:14 |
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