Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses

Clin Vaccine Immunol. 2017 Sep 5;24(9):e00157-17. doi: 10.1128/CVI.00157-17. Print 2017 Sep.

Abstract

This is the second phase 1 study of a respiratory syncytial virus (RSV) vaccine containing RSV fusion protein (sF) adjuvanted with glucopyranosyl lipid A (GLA) in a squalene-based 2% stable emulsion (GLA-SE). In this randomized, double-blind study, 261 subjects aged ≥60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 μg sF with escalating doses of GLA (1, 2.5, or 5 μg) in SE, or a vaccine containing 80 μg sF with 2.5 μg GLA in SE. Subjects receiving 120 μg sF with 2.5 or 5 μg GLA were also randomized to receive IIV or placebo. Immunity to RSV was assessed by detection of microneutralizing, anti-F immunoglobulin G, and palivizumab-competitive antibodies and F-specific gamma interferon enzyme-linked immunosorbent spot assay T-cell responses. Higher adjuvant doses increased injection site discomfort, but at the highest dose, the reactogenicity was similar to that of IIV. Significant humoral and cellular immune responses were observed. The 120 μg sF plus 5.0 μg GLA formulation resulted in the highest responses in all subjects and in older subjects. These results confirm previous observations of vaccine tolerability, safety, and immunogenicity and were used to select the 120 μg sF plus 5.0 μg GLA formulation for phase 2 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT02289820.).

Keywords: TLR-4 agonist; adjuvant; adult; cell-mediated immunity; respiratory syncytial virus; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Enzyme-Linked Immunospot Assay
  • Female
  • Glucosides / immunology*
  • Humans
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Immunogenicity, Vaccine
  • Immunoglobulin G / blood
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology
  • Influenza, Human / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Lipid A / immunology*
  • Male
  • Middle Aged
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Vaccines / administration & dosage
  • Respiratory Syncytial Virus Vaccines / chemistry
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology*
  • T-Lymphocytes / immunology
  • Viral Fusion Proteins / administration & dosage
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • F protein, human respiratory syncytial virus
  • Glucosides
  • Immunoglobulin G
  • Influenza Vaccines
  • Lipid A
  • Respiratory Syncytial Virus Vaccines
  • Viral Fusion Proteins
  • glucopyranosyl lipid-A
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT02289820