title: Safety and immunogenicity of dry powder measles vaccine administered by inhalation: a randomized controlled Phase I clinical trial.
abstract: BACKGROUND
  Measles is a highly infectious respiratory disease which causes 122,000 deaths annually. Although measles vaccine is extremely safe and effective, vaccine coverage could be improved by a vaccine that is more easily administered and transported. We developed an inhalable dry powder measles vaccine (MVDP) and two delivery devices, and demonstrated safety, immunogenicity, and efficacy of the vaccine in preclinical studies. Here we report the first clinical trial of MVDP delivered by inhalation.
  
  
  METHODS
  Sixty adult males aged 18 to 45 years, seropositive for measles antibody, were enrolled in this controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive either MVDP by Puffhaler(®) or by Solovent™ devices or the licensed subcutaneous measles vaccine. Adverse events (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followed for 180 days post-vaccination to assess potential serious long term adverse events. Measles antibody was measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaque reduction neutralization test.
  
  
  RESULTS
  All subjects completed the study according to protocol. Most subjects had high levels of baseline measles antibody. No adverse events were reported. MVDP produced serologic responses similar to subcutaneous vaccination.
  
  
  CONCLUSIONS
  MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibody titer which limited ability to measure the serologic responses, and may have limited the adverse events following vaccination. Additional studies in subjects without pre-existing measles antibody are needed to further elucidate the safety and immunogenicity of MVDP.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cape
authors.forename: Amol
authors.initials: A
authors.lastname: Chaudhari
authors.forename: Vivek
authors.initials: V
authors.lastname: Vaidya
authors.forename: Ravindra
authors.initials: R
authors.lastname: Mulay
authors.forename: Shalaka
authors.initials: S
authors.lastname: Agarkhedkar
authors.forename: Charles
authors.initials: C
authors.lastname: Shermer
authors.forename: Marcus
authors.initials: M
authors.lastname: Collins
authors.forename: Raydel
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Padmashri D Y Patil Medical College, Pune, India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Agarkhedkar
authors.affiliation: Serum Institute of India Ltd, Pune, India. Electronic address: drpsk@seruminstitute.com.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Kulkarni
authors.affiliation: AktivDry LLC, Boulder, CO, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Winston
authors.affiliation: AktivDry LLC, Boulder, CO, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sievers
authors.affiliation: Serum Institute of India Ltd, Pune, India.
authors.forename: Rajeev M
authors.initials: RM
authors.lastname: Dhere
authors.affiliation: Serum Institute of India Ltd, Pune, India.
authors.forename: Bhagwat
authors.initials: B
authors.lastname: Gunale
authors.affiliation: Becton Dickinson & Co., East Rutherford, NJ, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Powell
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Papania
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008457:Measles / Q000276:immunology / Q000517:prevention & control*; D008458:Measles Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008875:Middle Aged; D009500:Neutralization Tests; D011208:Powders / Q000008:administration & dosage* / Q000009:adverse effects*; D010948:Viral Plaque Assay; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D008458:Measles Vaccine; D011208:Powders
keywords: Dry powder measles vaccine; Immunogenicity; Inhalation; Respiratory administration; Safety; Subcutaneous measles vaccine