Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine

Vollmar, Jens; Arndtz, Nathaly; Eckl, Karl M.; Thomsen, T.; Petzold, Barbara; Mateo, Luis; Schlereth, Bernd; Handley, Amanda; King, Lynette T.; Hülsemann, Vanessa; Tzatzaris, Maria; Merkl, Karin; Wulff, Niels; Chaplin, Paul

doi:10.1016/j.vaccine.2005.11.022

Cited by 157 publications

(148 citation statements)

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“…Slightly fewer cases of erythema and induration were observed after the first or second IMVAMUNE ® injections given IM compared to SC. In a recent trial [9] to evaluate two doses of IMVAMUNE ® given subcutaneously or intramuscularly on Days 0 and 28, IMVAMUNE ® was found to be generally well-tolerated albeit, a higher incidence of systemic symptoms was reported in the IM versus the SC group. IMVAMUNE ® given prior to Dryvax ® reduces virus replication at the site of vaccination, local reactogenicity and the time to healing.…”

Section: Discussionmentioning

confidence: 99%

“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In a recent study, IMVAMUNE ® , a highly attenuated vaccinia strain derived from MVA-572 (obtained from Dr. Anton Mahr), does not replicate in human cells and was safe and immunogenic in humans [9]. The present study sought to evaluate the safety and immunogenicity of a range of doses and routes of administration of IMVAMUNE ® .…”

Section: Introductionmentioning

confidence: 99%

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Clinical and immunologic responses to multiple doses of IMVAMUNE® (Modified Vaccinia Ankara) followed by Dryvax® challenge

Frey

Newman

Kennedy

et al. 2007

Vaccine

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109

115

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Smallpox vaccination with replication deficient vaccinia strains such as Modified Vaccinia-Ankara (MVA) may induce protective immunity with improved safety and tolerability profiles compared with currently available smallpox vaccines. Ninety subjects were randomized equally to 6 groups in a partially blinded, randomized control clinical trial. IMVAMUNE ® (MVA-BN ® , Bavarian Nordic A/S, Kvistgård, Denmark) vaccine or placebo was administered at Study Day 0 and 28 by subcutaneous or intramuscular injection and five groups were challenged with Dryvax ® at study Day 112. Vaccination with two doses of IMVAMUNE ® was safe and well-tolerated compared to Dryvax ® . IMVAMUNE ® produced comparable cellular and humoral immune responses to one dose of Dryvax ® and the immunity induced appears robust 90 days post vaccination by evidence of attenuated primary cutaneous reaction responses following Dryvax ® . IMVAMUNE ® vaccination prior to Dryvax ® reduced virus replication at the Dryvax ® site, decreased the size of the primary cutaneous lesion, and decreased the time to healing but did not completely ameliorate the immune response. MO 63110,, E-mail address: E-mail: freyse@slu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In a recent study, IMVAMUNE ® , a highly attenuated vaccinia strain derived from MVA-572 (obtained from Dr. Anton Mahr), does not replicate in human cells and was safe and immunogenic in humans [9]. The present study sought to evaluate the safety and immunogenicity of a range of doses and routes of administration of IMVAMUNE ® . Potential surrogate efficacy of MVA-induced immune responses was evaluated by the ability of two doses of IMVAMUNE ® to reduce the clinical effects of a Dryvax ® challenge. Keywords NIH Public Access Author Manuscript Methods Vaccines and DiluentsIMVAMUNE ® (Bavarian Nordic A/S, Kvistgård, Denmark), a modified vaccinia Ankara vaccine (lot no. 130303), is a non-replicating virus in human cells used as the MVA smallpox vaccine in this study. Lyophilized vaccine was reconstituted with sterile water for injection (WFI) (Impfstoffwerk Dessau-Thornau GmbH, Germany). The reconstituted vaccine contains approximately 2 × 10 8 TCID 50 per ml. The placebo was sterile saline for injection (American Regent Laboratories, Inc, Shirley, NY). Licensed smallpox vaccine (Dryvax ® , Wyeth Laboratories, Marietta, PA) (lot no. 4008284), a replicating vaccinia virus provided by the Centers for Disease Control and Prevention in Atlanta, GA, was used as both the comparator vaccine and the virus in the challenge portion of this study.Reconstituted IM...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical and immunologic responses to multiple doses of IMVAMUNE® (Modified Vaccinia Ankara) followed by Dryvax® challenge

Frey

Newman

Kennedy

et al. 2007

Vaccine

Self Cite

109

115

View full text Add to dashboard Cite

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“…However, these highly effective vaccines are also associated with adverse events (AEs), including fever, headache, malaise, and in rare instances myopericarditis, post-vaccinal encephalitis, generalized vaccinia, and eczema vaccinatum, making them unsuitable for use in some populations, including infants, individuals who are immune compromised, and individuals with atopic dermatitis (11,17,21,31). A better understanding of immune responses to VACV could facilitate development of a new generation of vaccines that retain similar immunogenic profiles to the pre-eradication vaccines, but are modified to reduce the incidence of AEs following vaccination.…”

Section: Introductionmentioning

confidence: 99%

Correlations Between Vaccinia-Specific Immune Responses Within a Cohort of Armed Forces Members

et al. 2011

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Widespread vaccination with vaccinia virus (VACV) resulted in the eradication of smallpox; however, the licensed VACV-containing vaccines are associated with adverse events (AEs), making them unsuitable for certain high-risk populations. A better understanding of the host immune response following smallpox vaccination could result in vaccines with similar immunogenicity profiles to pre-eradication vaccines with a lower incidence of AEs. To study the immune response to VACV, we recruited 1,076 armed forces members who had been vaccinated with one dose of Dryvax Ò . We measured multiple VACV-specific immune responses: neutralizing antibody titer, the level of 12 secreted cytokines in peripheral blood mononuclear cell (PBMC) cultures (IL-1b, IL-2, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, TNF-a, IFN-c, IFN-a, , and the number of IFNc-and CD8 + IFN-c-secreting cells. We analyzed these data to determine correlations between immune response measures. We detected a strong proinflammatory response in concert with a Th-1-like cytokine response pattern at a median time point of 15.3 mo following primary vaccination. We also detected correlations between neutralizing antibody titer and secreted IL-2, as well as secreted IFN-c ( p = 0.009 and p = 0.0007, respectively). We also detected strong correlations between the proinflammatory cytokines IL-1b, TNF-a, IL-6, and IL-12p40 ( p < 0.0001). These results further advance our knowledge of vaccinia-specific cellular immune responses. Notably, vaccine-induced proinflammatory responses were not correlated with neutralizing antibody titers, suggesting that further attenuation to reduce inflammatory immune responses may result in decreased AEs without sacrificing VACV immunogenicity and population seropositivity.

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“…This study examined the historic vaccine used in the USA (Dryvax) and evaluated the humoral neutralizing-antibody responses elicited against variola virus. Additionally, this study evaluated the immune response elicited by one of the more recently developed (Stickl et al, 1974;Meyer et al, 1991;Vollmar et al, 2006), replication-impaired, less reactogenic smallpox vaccines, modified vaccinia virus Ankara (MVA) (Antoine et al, 1998;Vollmar et al, 2006); in this study, IMVAMUNE was used. Less reactogenic smallpox vaccines are anticipated to have fewer overall adverse events, especially those associated with direct virus replication (such as eczema vaccinatum, contact transmission and secondary-site implantation), associated with their use (Lane & Goldstein, 2003).…”

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confidence: 99%

Evaluation of smallpox vaccines using variola neutralization

Damon

Davidson

Hughes

et al. 2009

Journal of General Virology

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The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific ‘in vitro’ activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

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Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine

Cited by 157 publications

References 14 publications

Clinical and immunologic responses to multiple doses of IMVAMUNE® (Modified Vaccinia Ankara) followed by Dryvax® challenge

Clinical and immunologic responses to multiple doses of IMVAMUNE® (Modified Vaccinia Ankara) followed by Dryvax® challenge

Correlations Between Vaccinia-Specific Immune Responses Within a Cohort of Armed Forces Members

Evaluation of smallpox vaccines using variola neutralization

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