An inactivated Ross River virus vaccine is well tolerated and immunogenic in an adult population in a randomized phase 3 trial

Abstract

Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. More than 90,000 cases of RRV disease, which is characterized by debilitating polyarthritis, were reported in Australia in the last 20 years. There is no vaccine available to prevent RRV disease. A phase 3 study was undertaken at 17 sites in Australia to investigate the safety and immunogenicity of an inactivated whole-virus Vero cell culture-derived RRV vaccine in 1,755 healthy younger adults aged 16 to 59 years and 209 healthy older adults aged ≥60 years. Participants received a 2.5-μg dose of Al(OH)(3)-adjuvanted RRV vaccine, with a second and third dose after 3 weeks and 6 months, respectively. Vaccine-induced RRV-specific neutralizing and total IgG antibody titers were measured after each immunization. Vaccine safety was monitored over the entire study period. The vaccine was safe and well-tolerated after each vaccination. No cases of arthritis resembling RRV disease were reported. The most frequently reported systemic reactions were headache, fatigue, and malaise; the most frequently reported injection site reactions were tenderness and pain. After the third immunization, 91.5% of the younger age group and 76.0% of the older age group achieved neutralizing antibody titers of ≥1:10; 89.1% of the younger age group and 70.9% of the older age group achieved enzyme-linked immunosorbent assay (ELISA) titers of ≥11 PanBio units. A whole-virus Vero cell culture-derived RRV vaccine is well tolerated in an adult population and induces antibody titers associated with protection from RRV disease in the majority of individuals. (This study is registered at www.clinicaltrials.gov under registration no. NCT01242670.).

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Figures

FIG 1

Study profile.

FIG 2

Systemic and injection site reactions occurring within 7 days after each immunization. Data are the percentage of participants with mild, moderate, and severe reactions within 7 days after the first (1), second (2), and third (3) immunizations.

FIG 3

Neutralizing antibody responses. Geometric mean titer (GMT) of the μNT responses (A) and percentage of participants with μNT titers of ≥1:10 (B) at baseline (day 1), 3 weeks after the first immunization (day 22), 3 weeks after the second immunization (day 43), 6 months after the first immunization (day 181), and 3 weeks after the third immunization (day 202).

FIG 4

Reverse cumulative distributions of neutralizing antibody responses. Data are the percentage of participants with μNT titers above each titer cutoff at baseline (day 1), 3 weeks after the second immunization (day 43), and 3 weeks after the third immunization (day 202) in participants aged 16 to 59 years (A) and participants aged ≥60 years (B).

FIG 5

Total IgG ELISA antibody responses. Geometric mean titer (GMT) of total IgG ELISA (PBU) responses (A) and percentage of participants with ELISA titers of ≥11 PBU (B) at baseline (day 1), 3 weeks after the first immunization (day 22), 3 weeks after the second immunization (day 43), 6 months after the first immunization (day 181), and 3 weeks after the third immunization (day 202).