Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: A randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial
Autor(es): Ramsauer Katrin, Schwameis Michael, Firbas Christa, Müllner Matthias, Putnak Robert J, Thomas Stephen J, Desprès Philippe, Tauber Erich, Jilma Bernd, Tangy Frederic
Resumo: Chikungunya is an emerging arthropod-borne disease that has spread from tropical endemic areas to more temperate climates of the USA - Europe. However, no specific treatment or preventive measure is yet available. We aimed to investigate the immunogenicity - safety of a live recombinant measles-virus-based chikungunya vaccine. We did a r-omised, double-blind, placebo-controlled, active-comparator, phase 1, dose-escalation study at one centre in Vienna, Austria. Healthy men - women aged 18-45 years with no comorbidities were r-omly assigned, by computer-generated block r-omisation (block size of 14), to receive either one of three escalating doses of the measles-virus-based c-idate vaccine (low dose [1·5 × 10(4) median tissue culture infection doses (TCID50) per 0·05 mL], medium dose [7·5 × 10(4) TCID50 per 0·25 mL], or high dose [3·0 × 10(5) TCID50 per 1·0 mL]), or the active comparator-Priorix. Participants were additionally block-r-omised to receive a booster injection on either day 28 or day 90 after the first vaccination. Participants - study investigators were masked to group allocation. The primary endpoint was the presence of neutralising anti-chikungunya antibodies on day 28, as assessed by 50% plaque reduction neutralisation test. Analysis was by intention to treat - per protocol. This trial is registered with EudraCT, number 2013-001084-23. Between Nov 22, 2013, - Feb 25, 2014, we r-omly assigned 42 participants to receive the low dose (n=12), the medium dose (n=12), or the high dose (n=12) of the measles-virus-based c-idate vaccine, or Priorix (n=6), of whom 36 participants (86%; n=9, n=12, n=10, n=5, respectively) were included in the per-protocol population. The c-idate vaccine raised neutralising antibodies in all dose cohorts after one immunisation, with seroconversion rates of 44% (n=4) in the low-dose group, 92% (n=11) in the medium-dose group, - 90% (n=10) in the high-dose group. The immunogenicity of the c-idate vaccine was not affected by pre-existing anti-measles immunity. The second vaccination resulted in a 100% seroconversion for all participants in the c-idate vaccine groups. The c-idate vaccine had an overall good safety profile, - the rate of adverse events increased with vaccine dose - volume. No vaccination-related serious adverse events were recorded. The live recombinant measles-virus-based chikungunya vaccine had good immunogenicity, even in the presence of anti-vector immunity, was safe, - had a generally acceptable tolerability profile. This vaccine is the first promising measles-virus-based c-idate vaccine for use in human beings. Themis Bioscience GmBH.
Imprenta: The Lancet. Infectious Diseases, v. 15, n. 5, p. 519-527, 2015
Identificador do objeto digital: 10.1016/S1473-3099(15)70043-5
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2015
