Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.
A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP1(42), with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30) volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP1(42). Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted.


BACKGROUND
Clinicaltrials.gov NCT00889616.
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Rockville, Maryland, United States of America.
Ruth D
RD
Ellis
Yimin
Y
Wu
Laura B
LB
Martin
Donna
D
Shaffer
Kazutoyo
K
Miura
Joan
J
Aebig
Andrew
A
Orcutt
Kelly
K
Rausch
Daming
D
Zhu
Anders
A
Mogensen
Michael P
MP
Fay
David L
DL
Narum
Carole
C
Long
Louis
L
Miller
Anna P
AP
Durbin
D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C090077:apical membrane antigen I, Plasmodium; D000536:Aluminum Hydroxide