Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine.
Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 10(5) PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. rseder@mail.nih.gov
Robert A
RA
Seder
Lee-Jah
LJ
Chang
Mary E
ME
Enama
Kathryn L
KL
Zephir
Uzma N
UN
Sarwar
Ingelise J
IJ
Gordon
LaSonji A
LA
Holman
Eric R
ER
James
Peter F
PF
Billingsley
Anusha
A
Gunasekera
Adam
A
Richman
Sumana
S
Chakravarty
Anita
A
Manoj
Soundarapandian
S
Velmurugan
MingLin
M
Li
Adam J
AJ
Ruben
Tao
T
Li
Abraham G
AG
Eappen
Richard E
RE
Stafford
Sarah H
SH
Plummer
Cynthia S
CS
Hendel
Laura
L
Novik
Pamela J M
PJ
Costner
Floreliz H
FH
Mendoza
Jamie G
JG
Saunders
Martha C
MC
Nason
Jason H
JH
Richardson
Jittawadee
J
Murphy
Silas A
SA
Davidson
Thomas L
TL
Richie
Martha
M
Sedegah
Awalludin
A
Sutamihardja
Gary A
GA
Fahle
Kirsten E
KE
Lyke
Matthew B
MB
Laurens
Mario
M
Roederer
Kavita
K
Tewari
Judith E
JE
Epstein
B Kim Lee
BK
Sim
Julie E
JE
Ledgerwood
Barney S
BS
Graham
Stephen L
SL
Hoffman
D061605:Administration, Intravenous; D000328:Adult; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
D016207:Cytokines; D017780:Malaria Vaccines