Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine

• Published in: Nature communications Vol. 13; no. 1; pp. 1603 - 10
• Main Authors: Arévalo-Herrera, Myriam, Gaitán, Xiomara, Larmat-Delgado, Michelle, Caicedo, María Alejandra, Herrera, Sonia M., Henao-Giraldo, Juliana, Castellanos, Angélica, Devaud, Jean-Christophe, Pannatier, André, Oñate, José, Corradin, Giampietro, Herrera, Sócrates
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/590/2030; 692/308/2779/777; 692/699/255/1629; 82/1; Antibodies; Antibodies, Protozoan; Circumsporozoite protein; Clinical trials; Humanities and Social Sciences; Humans; Immunization; Immunoglobulin G; Malaria; Malaria Vaccines; Mineral Oil; multidisciplinary; Parasitemia; Plasmodium vivax; Protozoan Proteins; Science; Science (multidisciplinary); Subgroups; Vaccination; Vaccines; Vaccines, Synthetic; Vector-borne diseases; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29226-3

A randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of the Plasmodium vivax circumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants ( n  = 35) were randomly selected from a larger group ( n  = 121) and further divided into naïve ( n  = 17) and semi-immune ( n  = 18) groups and were immunized at months 0, 2, and 6 with Pv CS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses to Pv CS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25–0.84) and phase IIb (7/11) (64%, 95% CI 0.35–0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging further Pv CS vaccine clinical development. Trial registration number NCT 02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206). In this phase 2 clinical trial, the authors assess protective efficacy of a Plasmodium vivax circumsporozoite vaccine in naïve and semi-immune individuals from controlled human malaria infection as well as antibody and IFN-γ response to vaccination.