title: Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults.
abstract: Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population.
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Kawsar R
authors.initials: KR
authors.lastname: Talaat
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Hurd
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Autumn
authors.initials: A
authors.lastname: Hentrich
authors.affiliation: Biostatistical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: Gabriel
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.|Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Noreen A
authors.initials: NA
authors.lastname: Hynes
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Rausch
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Daming
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Olga
authors.initials: O
authors.lastname: Muratova
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Raul
authors.initials: R
authors.lastname: Herrera
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Joan
authors.initials: J
authors.lastname: Aebig
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brockley
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: MacDonald
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biostatistical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Healy
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000915:Antibody Affinity / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017780:Malaria Vaccines / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000009:adverse effects / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C099774:transmission-Blocking Vaccine based on Pfs25