A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE (original) (raw)
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Vaccine, 2013
Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses. Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination. The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0+7, Group: 0+28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0+7, Group: 0+28, and Group:...
PloS one, 2016
Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. ...
Dose-Related Effects of Smallpox Vaccine
New England Journal of Medicine, 2002
We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferong -producing T cells.
Clinical and immune response to undiluted and diluted smallpox vaccine
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology
0 0 8 ; 1 3 8 (2 7 – 2 8) : 3 9 2 – 3 9 7 · w w w . s m w . ch Question under study: To assess clinical reac-tions, immune responses and adverse events to undiluted, three-and sixfold diluted Lister strain vaccine stockpiled in Switzerland. Methods: A prospective, triple-blinded, ran-domised, parallel group clinical trial was per-formed. Results: From 2001 to 2007 104 persons with an indication for vaccinia vaccination were re-cruited. They had a median age of 33 years (range 18–65), 56 (53.8%) were re-vaccinees and 48 (46.2%) primary vaccinees. There was no statisti-cally significant variation in the proportion of re-vaccinees between diluted and undiluted vaccine groups (75% vs 51%, p = 0.118). With an overall clinical take rate (major reaction) of 97.1% the majority of the vaccinia-naïve participants exhib-ited an at least fourfold increase of neutralising antibody titres (32/38, 84.2%) post-vaccination. Interestingly this proportion was lower among re-vaccinees (29/46, 63.0%, p ...
Vaccine, 2010
A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers ଝ a b s t r a c t A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0 × 10 8 and 1.0 × 10 7 plaque-forming units/mL, respectively) (P > 0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243]. (M.-d. Oh).
PloS one, 2015
Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compar...
Smallpox: clinical highlights and considerations for vaccination
Journal of postgraduate medicine
Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia) vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.
Open Forum Infectious Diseases, 2015
Background. First-and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replicationdeficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.