Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects

Stuart P. Adler, Nicole Lewis, Anthony Conlon, Mark P. Christiansen, Mohamed Al-Ibrahim, Richard Rupp, Tong Ming Fu, Oliver Bautista, Huaping Tang, Dai Wang, Alison Fisher, Timothy Culp, Rituparna Das, Karen Beck, Gretchen Tamms, Luwy Musey

Research output: Contribution to journalArticle

Abstract

A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results: V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions: V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration:. NCT01986010.

Original languageEnglish (US)
Article numberjiz141
Pages (from-to)411-419
Number of pages9
JournalJournal of Infectious Diseases
Volume220
Issue number3
DOIs
StatePublished - Jul 2 2019

Fingerprint

Cytomegalovirus Vaccines
Clinical Trials, Phase I
Cytomegalovirus
Virus Shedding
Vaccines
Neutralizing Antibodies
Viral Nonstructural Proteins
Placebos
Viral Structural Proteins
Safety
Enzyme-Linked Immunospot Assay
Injections
Viral Genes
Cytomegalovirus Infections
Interferon-gamma
Clinical Trials
Viruses
T-Lymphocytes

Keywords

  • cytomegalovirus
  • immunogenicity
  • safety
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. / Adler, Stuart P.; Lewis, Nicole; Conlon, Anthony; Christiansen, Mark P.; Al-Ibrahim, Mohamed; Rupp, Richard; Fu, Tong Ming; Bautista, Oliver; Tang, Huaping; Wang, Dai; Fisher, Alison; Culp, Timothy; Das, Rituparna; Beck, Karen; Tamms, Gretchen; Musey, Luwy.

In: Journal of Infectious Diseases, Vol. 220, No. 3, jiz141, 02.07.2019, p. 411-419.

Research output: Contribution to journalArticle

Adler, SP, Lewis, N, Conlon, A, Christiansen, MP, Al-Ibrahim, M, Rupp, R, Fu, TM, Bautista, O, Tang, H, Wang, D, Fisher, A, Culp, T, Das, R, Beck, K, Tamms, G & Musey, L 2019, 'Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects', Journal of Infectious Diseases, vol. 220, no. 3, jiz141, pp. 411-419. https://doi.org/10.1093/infdis/jiz141
Adler, Stuart P. ; Lewis, Nicole ; Conlon, Anthony ; Christiansen, Mark P. ; Al-Ibrahim, Mohamed ; Rupp, Richard ; Fu, Tong Ming ; Bautista, Oliver ; Tang, Huaping ; Wang, Dai ; Fisher, Alison ; Culp, Timothy ; Das, Rituparna ; Beck, Karen ; Tamms, Gretchen ; Musey, Luwy. / Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. In: Journal of Infectious Diseases. 2019 ; Vol. 220, No. 3. pp. 411-419.
@article{cabd4b8c5e8c44b8bd6200d886d23b43,
title = "Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects",
abstract = "A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results: V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions: V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration:. NCT01986010.",
keywords = "cytomegalovirus, immunogenicity, safety, vaccine",
author = "Adler, {Stuart P.} and Nicole Lewis and Anthony Conlon and Christiansen, {Mark P.} and Mohamed Al-Ibrahim and Richard Rupp and Fu, {Tong Ming} and Oliver Bautista and Huaping Tang and Dai Wang and Alison Fisher and Timothy Culp and Rituparna Das and Karen Beck and Gretchen Tamms and Luwy Musey",
year = "2019",
month = "7",
day = "2",
doi = "10.1093/infdis/jiz141",
language = "English (US)",
volume = "220",
pages = "411--419",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects

AU - Adler, Stuart P.

AU - Lewis, Nicole

AU - Conlon, Anthony

AU - Christiansen, Mark P.

AU - Al-Ibrahim, Mohamed

AU - Rupp, Richard

AU - Fu, Tong Ming

AU - Bautista, Oliver

AU - Tang, Huaping

AU - Wang, Dai

AU - Fisher, Alison

AU - Culp, Timothy

AU - Das, Rituparna

AU - Beck, Karen

AU - Tamms, Gretchen

AU - Musey, Luwy

PY - 2019/7/2

Y1 - 2019/7/2

N2 - A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results: V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions: V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration:. NCT01986010.

AB - A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results: V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions: V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration:. NCT01986010.

KW - cytomegalovirus

KW - immunogenicity

KW - safety

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85070073948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070073948&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiz141

DO - 10.1093/infdis/jiz141

M3 - Article

VL - 220

SP - 411

EP - 419

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

M1 - jiz141

ER -