PMID- 31535143
OWN - NLM
STAT- MEDLINE
DCOM- 20200221
LR  - 20200221
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 220
IP  - 3
DP  - 2019 Jul 2
TI  - Phase 1 Clinical Trial of a Conditionally Replication-Defective Human 
      Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects.
PG  - 411-419
LID - 10.1093/infdis/jiz141 [doi]
AB  - BACKGROUND: 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.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Adler, Stuart P
AU  - Adler SP
AD  - CMV Research Foundation, Richmond, Virginia.
FAU - Lewis, Nicole
AU  - Lewis N
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Conlon, Anthony
AU  - Conlon A
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Christiansen, Mark P
AU  - Christiansen MP
AD  - Diablo Clinical Research Inc., Walnut Creek, California.
FAU - Al-Ibrahim, Mohamed
AU  - Al-Ibrahim M
AD  - SNBL Clinical Pharmacology Center, Baltimore, Maryland.
FAU - Rupp, Richard
AU  - Rupp R
AD  - Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, 
      Galveston, Texas.
FAU - Fu, Tong-Ming
AU  - Fu TM
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Bautista, Oliver
AU  - Bautista O
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Tang, Huaping
AU  - Tang H
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Wang, Dai
AU  - Wang D
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Fisher, Alison
AU  - Fisher A
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Culp, Timothy
AU  - Culp T
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Das, Rituparna
AU  - Das R
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Beck, Karen
AU  - Beck K
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Tamms, Gretchen
AU  - Tamms G
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
FAU - Musey, Luwy
AU  - Musey L
AD  - Merck & Co., Inc., Kenilworth, New Jersey.
CN  - V160-001 Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT01986010
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Cytomegalovirus Vaccines)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Neutralizing/immunology
MH  - Antibodies, Viral/immunology
MH  - Cytomegalovirus/*immunology
MH  - Cytomegalovirus Infections/*immunology
MH  - Cytomegalovirus Vaccines/*immunology
MH  - Double-Blind Method
MH  - Enzyme-Linked Immunospot Assay/methods
MH  - Female
MH  - Humans
MH  - Immunity, Cellular/immunology
MH  - Immunity, Humoral/immunology
MH  - Immunization/methods
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/immunology
MH  - Vaccination/methods
MH  - Virus Replication/*immunology
MH  - Virus Shedding/immunology
MH  - Young Adult
OTO - NOTNLM
OT  - cytomegalovirus
OT  - immunogenicity
OT  - safety
OT  - vaccine
EDAT- 2019/09/20 06:00
MHDA- 2020/02/23 06:00
CRDT- 2019/09/20 06:00
PHST- 2018/12/20 00:00 [received]
PHST- 2019/04/10 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
AID - 5527176 [pii]
AID - 10.1093/infdis/jiz141 [doi]
PST - ppublish
SO  - J Infect Dis. 2019 Jul 2;220(3):411-419. doi: 10.1093/infdis/jiz141.