Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults

Vaccine. 2015 Jul 17;33(31):3766-72. doi: 10.1016/j.vaccine.2015.05.024. Epub 2015 Jun 8.

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.

Clinical trials registration: NCT01764256.

Keywords: Diarrhea; Non-replicating; Parenteral; Rotavirus; Subunit; Vaccine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage
  • Antibodies, Neutralizing / blood
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gastroenteritis / prevention & control*
  • Healthy Volunteers
  • Humans
  • Immunoglobulin A / analysis
  • Immunoglobulin A / blood
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Neutralization Tests
  • Placebos / administration & dosage
  • RNA-Binding Proteins / immunology*
  • Rotavirus Infections / prevention & control*
  • Rotavirus Vaccines / administration & dosage
  • Rotavirus Vaccines / adverse effects*
  • Rotavirus Vaccines / immunology*
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Viral Nonstructural Proteins / immunology*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Immunoglobulin A
  • Immunoglobulin G
  • Placebos
  • RNA-Binding Proteins
  • Rotavirus Vaccines
  • Vaccines, Subunit
  • Viral Nonstructural Proteins
  • NS35 protein, rotavirus
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT01764256