title: Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria.
abstract: Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Washington, DC 20307, USA. LTC_Chris_Ockenhouse@wrsmtp-ccmail.army.mil
authors.forename: C F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: P F
authors.initials: PF
authors.lastname: Sun
authors.forename: D E
authors.initials: DE
authors.lastname: Lanar
authors.forename: B T
authors.initials: BT
authors.lastname: Wellde
authors.forename: B T
authors.initials: BT
authors.lastname: Hall
authors.forename: K
authors.initials: K
authors.lastname: Kester
authors.forename: J A
authors.initials: JA
authors.lastname: Stoute
authors.forename: A
authors.initials: A
authors.lastname: Magill
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: L
authors.initials: L
authors.lastname: Farley
authors.forename: R A
authors.initials: RA
authors.lastname: Wirtz
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: L W
authors.initials: LW
authors.lastname: Church
authors.forename: J M
authors.initials: JM
authors.lastname: Crutcher
authors.forename: B
authors.initials: B
authors.lastname: Wizel
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: A
authors.initials: A
authors.lastname: Lalvani
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
authors.forename: J A
authors.initials: JA
authors.lastname: Tine
authors.forename: K P
authors.initials: KP
authors.lastname: Guito
authors.forename: C
authors.initials: C
authors.lastname: de Taisne
authors.forename: R
authors.initials: R
authors.lastname: Anders
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000009:adverse effects / Q000276:immunology*; D003257:Consumer Product Safety; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus; D014764:Viral Proteins / Q000009:adverse effects / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; C112460:NYVAC Pf7 vaccine; C078787:NYVAC vaccine; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines