Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing.
2021 Jan 22
Journal Article
Authors:
Friedman-Klabanoff, D.A.J.;
Berry, A.A.;
Travassos, M.A.;
Cox, C.;
Zhou, Y.;
Mo, A.X.;
Nomicos, E.Y.H.;
Deye, G.A.;
Pasetti, M.F.;
Laurens, M.B.
Secondary:
Vaccine
Volume:
S0264-410X(20)31590
PMID:
33494963
URL:
https://pubmed.ncbi.nlm.nih.gov/33494963/
DOI:
10.1016/j.vaccine.2020.12.023
Keywords:
Circumsporozoite protein; Malaria; Malaria vaccine; Plasmodium falciparum.
Abstract:
Plasmodium falciparum circumsporozoite protein (CSP) is a major sporozoite surface protein and a key target of pre-erythrocytic malaria subunit vaccines. A full-length recombinant CSP (rCSP) based strategy could be advantageous, as this antigen includes a region critical to sporozoite cell attachment and hepatocyte invasion. The adjuvant Glucopyranosyl Lipid A-liposome Quillaja saponaria 21 (GLA-LSQ) functions as a TLR4 agonist, promotes antigen-specific T1 responses and stimulates cytotoxic T cell production. To date, one study has reported the clinical acceptability of GLA-LSQ. We present interim results of a phase 1 first-in-human dose-escalation clinical trial of full-length rCSP vaccine given with or without GLA-LSQ adjuvant. Participants experienced only mild to moderate related solicited adverse events. The lowest adjuvanted vaccine dose achieved >90-fold rise in geometric mean anti-CSP IgG antibody titer. These favorable safety and immunogenicity results confirm the immunostimulatory capacity of this relatively new adjuvant and support next steps in clinical product development. Trial registration: ClinicalTrials.gov Identifier NCT03589794 (registered 18 July 2018).
