In:
The Journal of Infectious Diseases, Oxford University Press (OUP), ( 2024-02-08)
Abstract:
Malaria is preventable yet causes & gt;600,000 deaths annually. RTS, S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. Methods We conducted an open-label, dose escalation Phase 1 study of a recombinant, full-length circumsporozoite protein vaccine (rCSP) administered with adjuvant GLA-LSQ on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naïve adults. Primary endpoints were safety and reactogenicity. Secondary endpoints were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection (CHMI). Results Participants were enrolled into four groups receiving rCSP/GLA-LSQ: 10 µg x 3 (n = 20), 30 µg x 3 (n = 10), 60 µg x 3 (n = 10) or 60 µg x 2 (n = 9); ten participants received 30 µg rCSP alone x 3; and six infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent CHMI 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher IgG titers, but did not achieve previously established RTS, S benchmarks. Conclusions rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess if adjuvant or schedule adjustments improve efficacy. Trial registration ClinicalTrials.gov Identifier NCT03589794
Type of Medium:
Online Resource
ISSN:
0022-1899
,
1537-6613
DOI:
10.1093/infdis/jiae062
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
1473843-0
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