Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial.

Autor:	Blank A; 1Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany., Fürle K; 2Center of Infectious Diseases, Parasitology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany., Jäschke A; 2Center of Infectious Diseases, Parasitology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany., Mikus G; 1Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany., Lehmann M; 3Koordinierungszentrum für Klinische Studien (KKS), Universitätsklinikum Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany., Hüsing J; 3Koordinierungszentrum für Klinische Studien (KKS), Universitätsklinikum Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany., Heiss K; PEPperPRINT GmbH, Rischerstrasse 12, 69123 Heidelberg, Germany., Giese T; 5Institut für Immunologie, Universitätsklinikum Heidelberg und Deutsches Zentrum für Infektionsforschung (DZIF) Standort Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany., Carter D; 6PAI Life Sciences, 1616 Eastlake Ave E, Suite 550, Seattle, WA 98102 USA., Böhnlein E; Sumaya Biotech GmbH & Co. KG, Im Neuenheimer Feld 582, 69120 Heidelberg, Germany., Lanzer M; 2Center of Infectious Diseases, Parasitology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany., Haefeli WE; 1Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany., Bujard H; Sumaya Biotech GmbH & Co. KG, Im Neuenheimer Feld 582, 69120 Heidelberg, Germany.; 8Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2020 Jan 31; Vol. 5 (1), pp. 10. Date of Electronic Publication: 2020 Jan 31 (Print Publication: 2020).
DOI:	10.1038/s41541-020-0160-2
Abstrakt:	A vaccine remains a priority in the global fight against malaria. Here, we report on a single-center, randomized, double-blind, placebo and adjuvant-controlled, dose escalation phase 1a safety and immunogenicity clinical trial of full-length Plasmodium falciparum merozoite surface protein 1 (MSP1) in combination with GLA-SE adjuvant. Thirty-two healthy volunteers were vaccinated at least three times with MSP1 plus adjuvant, adjuvant alone, or placebo (24:4:4) to evaluate the safety and immunogenicity. MSP1 was safe, well tolerated and immunogenic, with all vaccinees sero-converting independent of the dose. The MSP1-specific IgG and IgM titers persisted above levels found in malaria semi-immune humans for at least 6 months after the last immunization. The antibodies were variant- and strain-transcending and stimulated respiratory activity in granulocytes. Furthermore, full-length MSP1 induced memory T-cells. Our findings encourage challenge studies as the next step to evaluate the efficacy of full-length MSP1 as a vaccine candidate against falciparum malaria (EudraCT 2016-002463-33). Competing Interests: Competing interestsH.B., E.B. and M.L. are shareholders of Sumaya GmbH & Co. KG. The other authors declare no competing interests. (© The Author(s) 2020.)
Databáze:	MEDLINE
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