title: Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine.
abstract: The malaria sporozoite vaccine candidate RTS,S, formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 (vaccine 3), recently showed superior efficacy over two other experimental formulations. Immunized volunteers were followed to determine the duration of protective immune responses. Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine. T cell proliferation and interferon-gamma production in vitro were observed in response to RTS,S or hepatitis B surface antigen. Seven previously protected volunteers received sporozoite challenge, and 2 remained protected (1/1 for vaccine 1, 0/1 for vaccine 2, and 1/5 for vaccine 3). The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees (P < .01). Immune responses did not correlate with protection. Further optimization in vaccine composition and/or immunization schedule will be required to induce longer-lasting protective immunity.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Washington, DC, USA. stoutej@wrsmtp-ccmail.army.mil
authors.forename: J A
authors.initials: JA
authors.lastname: Stoute
authors.forename: K E
authors.initials: KE
authors.lastname: Kester
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: B T
authors.initials: BT
authors.lastname: Wellde
authors.forename: T
authors.initials: T
authors.lastname: Hall
authors.forename: K
authors.initials: K
authors.lastname: White
authors.forename: G
authors.initials: G
authors.lastname: Glenn
authors.forename: C F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: N
authors.initials: N
authors.lastname: Garcon
authors.forename: R
authors.initials: R
authors.lastname: Schwenk
authors.forename: D E
authors.initials: DE
authors.lastname: Lanar
authors.forename: P
authors.initials: P
authors.lastname: Sun
authors.forename: P
authors.initials: P
authors.lastname: Momin
authors.forename: R A
authors.initials: RA
authors.lastname: Wirtz
authors.forename: C
authors.initials: C
authors.lastname: Golenda
authors.forename: M
authors.initials: M
authors.lastname: Slaoui
authors.forename: G
authors.initials: G
authors.lastname: Wortmann
authors.forename: C
authors.initials: C
authors.lastname: Holland
authors.forename: M
authors.initials: M
authors.lastname: Dowler
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D018572:Disease-Free Survival; D006801:Humans; D007371:Interferon-gamma; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008875:Middle Aged; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma