An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults

Christopher W. Woods, Ana M. Sanchez, Geeta K. Swamy, Micah T. McClain, Lynn Harrington, Debra Freeman, Elizabeth A. Poore, Dawn K. Slifka, Danae E. Poer DeRaad, Ian J. Amanna, Mark Slifka, Shu Cai, Venus Shahamatdar, Michael R. Wierzbicki, Cyrille Amegashie, Emmanuel B. Walter

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Background: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. Methods: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). Results: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA. Conclusions: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.

    Original languageEnglish (US)
    JournalVaccine
    DOIs
    StateAccepted/In press - Jan 1 2019

    Fingerprint

    West Nile Virus Vaccines
    West Nile virus
    Inactivated Vaccines
    placebos
    Placebos
    immune response
    vaccines
    Safety
    dosage
    seroconversion
    Enzyme-Linked Immunosorbent Assay
    enzyme-linked immunosorbent assay
    Aluminum Hydroxide
    Neutralization Tests
    complement
    Intramuscular Injections
    Neutralizing Antibodies
    Culicidae
    Virion
    Hydrogen Peroxide

    Keywords

    • Phase 1
    • Vaccine
    • West Nile virus

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

    Cite this

    An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults. / Woods, Christopher W.; Sanchez, Ana M.; Swamy, Geeta K.; McClain, Micah T.; Harrington, Lynn; Freeman, Debra; Poore, Elizabeth A.; Slifka, Dawn K.; Poer DeRaad, Danae E.; Amanna, Ian J.; Slifka, Mark; Cai, Shu; Shahamatdar, Venus; Wierzbicki, Michael R.; Amegashie, Cyrille; Walter, Emmanuel B.

    In: Vaccine, 01.01.2019.

    Research output: Contribution to journalArticle

    Woods, CW, Sanchez, AM, Swamy, GK, McClain, MT, Harrington, L, Freeman, D, Poore, EA, Slifka, DK, Poer DeRaad, DE, Amanna, IJ, Slifka, M, Cai, S, Shahamatdar, V, Wierzbicki, MR, Amegashie, C & Walter, EB 2019, 'An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults', Vaccine. https://doi.org/10.1016/j.vaccine.2018.12.026
    Woods, Christopher W. ; Sanchez, Ana M. ; Swamy, Geeta K. ; McClain, Micah T. ; Harrington, Lynn ; Freeman, Debra ; Poore, Elizabeth A. ; Slifka, Dawn K. ; Poer DeRaad, Danae E. ; Amanna, Ian J. ; Slifka, Mark ; Cai, Shu ; Shahamatdar, Venus ; Wierzbicki, Michael R. ; Amegashie, Cyrille ; Walter, Emmanuel B. / An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults. In: Vaccine. 2019.
    @article{7c06b82683164e35b688c39c043b50af,
    title = "An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults",
    abstract = "Background: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. Methods: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). Results: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41{\%} seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31{\%} of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50{\%}, and 75{\%} seroconversion was observed by WNV-specific ELISA. Conclusions: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.",
    keywords = "Phase 1, Vaccine, West Nile virus",
    author = "Woods, {Christopher W.} and Sanchez, {Ana M.} and Swamy, {Geeta K.} and McClain, {Micah T.} and Lynn Harrington and Debra Freeman and Poore, {Elizabeth A.} and Slifka, {Dawn K.} and {Poer DeRaad}, {Danae E.} and Amanna, {Ian J.} and Mark Slifka and Shu Cai and Venus Shahamatdar and Wierzbicki, {Michael R.} and Cyrille Amegashie and Walter, {Emmanuel B.}",
    year = "2019",
    month = "1",
    day = "1",
    doi = "10.1016/j.vaccine.2018.12.026",
    language = "English (US)",
    journal = "Vaccine",
    issn = "0264-410X",
    publisher = "Elsevier BV",

    }

    TY - JOUR

    T1 - An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults

    AU - Woods, Christopher W.

    AU - Sanchez, Ana M.

    AU - Swamy, Geeta K.

    AU - McClain, Micah T.

    AU - Harrington, Lynn

    AU - Freeman, Debra

    AU - Poore, Elizabeth A.

    AU - Slifka, Dawn K.

    AU - Poer DeRaad, Danae E.

    AU - Amanna, Ian J.

    AU - Slifka, Mark

    AU - Cai, Shu

    AU - Shahamatdar, Venus

    AU - Wierzbicki, Michael R.

    AU - Amegashie, Cyrille

    AU - Walter, Emmanuel B.

    PY - 2019/1/1

    Y1 - 2019/1/1

    N2 - Background: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. Methods: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). Results: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA. Conclusions: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.

    AB - Background: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. Methods: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). Results: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA. Conclusions: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.

    KW - Phase 1

    KW - Vaccine

    KW - West Nile virus

    UR - http://www.scopus.com/inward/record.url?scp=85060077789&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85060077789&partnerID=8YFLogxK

    U2 - 10.1016/j.vaccine.2018.12.026

    DO - 10.1016/j.vaccine.2018.12.026

    M3 - Article

    JO - Vaccine

    JF - Vaccine

    SN - 0264-410X

    ER -