Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naïve adults at the Walter Reed Army Institute of Research.
We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating Phase I trial in 23 malaria-naïve volunteers who received 8, 20 or 40microg of FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule. Nineteen of 23 volunteers received all three scheduled immunizations. The most frequent solicited local and systemic adverse events associated with immunization were injection site pain (68%) and headache (29%). There were no significant laboratory abnormalities or vaccine-related serious adverse events. All volunteers seroconverted after second immunization as determined by ELISA. Immune sera recognized sporozoites and merozoites by immunofluorescence assay (IFA), and exhibited both growth inhibition and processing inhibition activity against homologous (3D7) asexual stage parasites. Post-immunization, peripheral blood mononuculear cells exhibited FMP2.1-specific lymphoproliferation and IFN-gamma and IL-5 ELISPOT assay responses. This is the first PfAMA-1-based vaccine shown to elicit both potent humoral and cellular immunity in humans. Encouraged by the potential of FMP1/AS02A to target host immunity against PfAMA-1 that is known to be expressed by sporozoite, hepatic and erythrocytic stages, we have initiated field trials of FMP2.1/AS02A in an endemic population in the Republic of Mali.
Polhemus
Mark E
ME
Walter Reed Army Institute of Research, Silver Spring, MD, United States. mpolhemus@wrp-ksm.org
Magill
Alan J
AJ
Cummings
James F
JF
Kester
Kent E
KE
Ockenhouse
Chris F
CF
Lanar
David E
DE
Dutta
Sheetij
S
Barbosa
Arnoldo
A
Soisson
Lorraine
L
Diggs
Carter L
CL
Robinson
Sally A
SA
Haynes
John D
JD
Stewart
V Ann
VA
Ware
Lisa A
LA
Brando
Clara
C
Krzych
Urszula
U
Bowden
Robert A
RA
Cohen
Joe D
JD
Dubois
Marie-Claude
MC
Ofori-Anyinam
Opokua
O
De-Kock
Els
E
Ballou
W Ripley
WR
Heppner
D Gray
DG
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006261:Headache; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D052940:Merozoites / Q000276:immunology; D008647:Mesocricetus; D008875:Middle Aged; D010146:Pain; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004338:Drug Combinations; D015848:Interleukin-5; D008050:Lipid A; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D012503:Saponins; D014614:Vaccines, Synthetic; C090077:apical membrane antigen I, Plasmodium; D007371:Interferon-gamma