title: Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults.
abstract: BACKGROUND
  The P2-VP8 subunit vaccine for the prevention of rotavirus gastroenteritis is comprised of a truncated VP8 subunit protein from the rotavirus Wa strain (G1[P8]) fused to the tetanus toxin P2 epitope, and adsorbed on aluminum hydroxide for intramuscular administration.
  
  
  METHODS
  Three groups of 16 adults were randomized to receive three injections of P2-VP8 (12) or placebo (4) at doses of 10, 30 or 60 μg of vaccine. IgG and IgA antibodies to P2-VP8 were assessed by ELISA in serum and lymphocyte supernatant (ALS). Serum samples were tested for neutralizing antibodies to homologous and heterologous strains of rotavirus.
  
  
  RESULTS
  The vaccine was well-tolerated. All vaccine recipients demonstrated significant IgA responses and all but one demonstrated IgG responses; in the 60 μg cohort, geometric mean titers (GMTs) rose 70- and 80-fold for IgA and IgG, respectively. Homologous neutralizing antibody responses were observed in about half of participants in all three dose cohorts; in the 60 μg cohort, GMTs against Wa rose from 128 to 992. Neutralizing antibody responses were robust to P[8] strains, moderate to P[4] strains and negligible to P[6] strains. ALS IgA responses were dose dependent.
  
  
  CONCLUSIONS
  The P2-VP8 subunit vaccine was well tolerated and evoked promising immune responses.
  
  
  BACKGROUND
  NCT01764256.
authors.affiliation: Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: afix@path.org.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Fix
authors.affiliation: Center for Immunization Research, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, 624N. Broadway, Suite 117, Hampton House, Baltimore, MD 21205, USA.
authors.forename: Clayton
authors.initials: C
authors.lastname: Harro
authors.affiliation: Laboratory for Specialized Clinical Studies, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 333 Burnet Avenue ML6014, Cincinnati, OH, 45229, USA. Electronic address: Monica.McNeal@cchmc.org.
authors.forename: Monica
authors.initials: M
authors.lastname: McNeal
authors.affiliation: The EMMES Corporation, 401N. Washington Street, Suite 700, Rockville, MD, 20850, USA. Electronic address: ldally@emmes.com.
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.affiliation: Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: jeflores@path.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Flores
authors.affiliation: Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: grobertson@path.org.
authors.forename: George
authors.initials: G
authors.lastname: Robertson
authors.affiliation: Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: jboslego@path.org.
authors.forename: John W
authors.initials: JW
authors.lastname: Boslego
authors.affiliation: Vaccine Development Global Program, PATH, 455 Massachusetts Ave., Suite 1000, Washington, DC, 20001, USA. Electronic address: scryz@path.org.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cryz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D057134:Antibodies, Neutralizing / Q000097:blood; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control*; D064368:Healthy Volunteers; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007273:Injections, Intramuscular; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010919:Placebos / Q000008:administration & dosage; D016601:RNA-Binding Proteins / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010919:Placebos; D016601:RNA-Binding Proteins; D022243:Rotavirus Vaccines; D022223:Vaccines, Subunit; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus; D000536:Aluminum Hydroxide
keywords: Diarrhea; Non-replicating; Parenteral; Rotavirus; Subunit; Vaccine