title: Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study.
abstract: BACKGROUND
  Shigellae cause severe disease in endemic countries, especially in children. Several efficacy trials have been conducted with candidate vaccines against Shigellae, but the lack of protection, the safety concerns, or manufacturing challenges hindered successful market approval. Conjugated vaccines have been shown to be safe and effective for different pathogens (i.e., Neisseria meningitidis, Shigella pneumonia, Haemophilus influenzae). The bio-conjugation technology, exploited here for the Shigella dysenteriae candidate vaccine, offers a novel and potentially simpler way to develop and produce vaccines against one of the major causes of morbidity and mortality in developing countries.
  
  
  METHODS
  A novel S. dysenteriae bioconjugate vaccine (GVXN SD133) made of the polysaccharide component of the Shigella O1 lipopolysaccharide, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for immunogenicity and safety in healthy adults in a single blind, partially randomized Phase I study. Forty subjects (10 in each dose group; 2 μg or 10 μg with or without aluminium adjuvant) received two injections 60 days apart and were followed-up for 150 days.
  
  
  RESULTS
  Both doses and formulations were well tolerated; the safety and reactogenicity profiles were consistent with that of other conjugated vaccines, adjuvanted or not, independent of the dose and the number of injections. The GVXN SD133 vaccine elicited statistically significant O1 specific humoral responses at all time points in all vaccination groups. Between-group comparisons did not show statistically significant differences in geometric mean titers of immunoglobulin G and A at any post-vaccination time point.
  
  
  CONCLUSIONS
  This study demonstrated that the GVXN SD133 vaccine has a satisfactory safety profile. It elicited a significant humoral response to Shigella O1 polysaccharides at all doses tested. The protein carrier also elicited functional antibodies, showing the technology's advantages in preserving both sugar and conjugated protein epitopes. This trial is registered at ClinicalTrials.gov (NCT01069471).
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute (formerly Social and Preventive Medicine (ISPM), University of Zurich, Hirschengraben 84, Zurich 8001, Switzerland; Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
authors.forename: Christoph F R
authors.initials: CF
authors.lastname: Hatz
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute (formerly Social and Preventive Medicine (ISPM), University of Zurich, Hirschengraben 84, Zurich 8001, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bally
authors.affiliation: GlycoVaxyn AG, Grabenstrasse 3, Schlieren 8952, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rohrer
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute (formerly Social and Preventive Medicine (ISPM), University of Zurich, Hirschengraben 84, Zurich 8001, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Steffen
authors.affiliation: Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kramme
authors.affiliation: Center for Vaccinology, University of Geneva, CMU, 1 Michel-Servet, Geneva 4, Geneva 1211, Switzerland.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.affiliation: GlycoVaxyn AG, Grabenstrasse 3, Schlieren 8952, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Wacker
authors.affiliation: GlycoVaxyn AG, Grabenstrasse 3, Schlieren 8952, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alaimo
authors.affiliation: GlycoVaxyn AG, Grabenstrasse 3, Schlieren 8952, Switzerland. Electronic address: veronica.gambillara@glycovaxyn.com.
authors.forename: Veronica Gambillara
authors.initials: VG
authors.lastname: Fonck
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004337:Drug Carriers / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000517:prevention & control*; D005098:Exotoxins / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D019081:O Antigens / Q000276:immunology; D012762:Shigella dysenteriae / Q000276:immunology*; D016037:Single-Blind Method; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D037521:Virulence Factors / Q000378:metabolism; D055815:Young Adult; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004337:Drug Carriers; D005098:Exotoxins; D019081:O Antigens; D018074:Vaccines, Conjugate; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: Bioconjugate; Immunogenicity; Reactogenicity; Safety; Shigella; Vaccine