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.
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 TH1 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).
['Friedman-Klabanoff|DeAnna J|DJ|', 'Berry|Andrea A|AA|', 'Travassos|Mark A|MA|', 'Cox|Catherine|C|', 'Zhou|Yingjun|Y|', 'Mo|Annie X|AX|', 'Nomicos|Effie Y H|EYH|', 'Deye|Gregory A|GA|', 'Pasetti|Marcela F|MF|', 'Laurens|Matthew B|MB|']
D000818:Animals D000913:Antibodies, Protozoan D000917:Antibody Formation D006801:Humans D017780:Malaria Vaccines D016778:Malaria, Falciparum D010963:Plasmodium falciparum D015800:Protozoan Proteins D014614:Vaccines, Synthetic
Plasmodium falciparum Circumsporozoite protein Malaria Malaria vaccine