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

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, doubleblind study, 261 subjects aged >= 60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 mu g sF with escalating doses of GLA (1, 2.5, or 5 mu g) in SE, or a vaccine containing 80 mu g sF with 2.5 mu g GLA in SE. Subjects receiving 120 mu g sF with 2.5 or 5 mu g 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 enzymelinked 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 mu g sF plus 5.0 mu g 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 mu g sF plus 5.0 mu g GLA formulation for phase 2 evaluation.