title: Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.
abstract: BACKGROUND
  A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.
  
  
  METHODS
  We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.
  
  
  RESULTS
  The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.
  
  
  CONCLUSIONS
  This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bennett
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Donna
authors.initials: D
authors.lastname: Tosh
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jack
authors.initials: J
authors.lastname: Komisar
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ware
authors.affiliation: U.S. Army Medical Materiel Development Activity, Frederick, Maryland, United States of America.
authors.forename: William F
authors.initials: WF
authors.lastname: McCarthy
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Cowden
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Regules
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Michele D
authors.initials: MD
authors.lastname: Spring
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Paolino
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hartzell
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Cummings
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, United States of America.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lumsden
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Edwin
authors.initials: E
authors.lastname: Kamau
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jittawadee
authors.initials: J
authors.lastname: Murphy
authors.affiliation: PATH-MVI, Washington, D.C., United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lee
authors.affiliation: PATH-MVI, Washington, D.C., United States of America.
authors.forename: Falgunee
authors.initials: F
authors.lastname: Parekh
authors.affiliation: PATH-MVI, Washington, D.C., United States of America.
authors.forename: Ashley
authors.initials: A
authors.lastname: Birkett
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Polhemus
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Yannick F
authors.initials: YF
authors.lastname: Vanloubbeeck
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.affiliation: Malaria Vaccine Brach, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins