PMID- 19857446
OWN - NLM
STAT- MEDLINE
DCOM- 20100303
LR  - 20091204
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 28
IP  - 2
DP  - 2009 Dec 11
TI  - Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for 
      cytomegalovirus in CMV seronegative adult volunteers.
PG  - 484-93
LID - 10.1016/j.vaccine.2009.09.135 [doi]
AB  - Development of a cytomegalovirus (CMV) vaccine is a priority. We evaluated a two 
      component alphavirus replicon particle vaccine expressing CMV gB or a pp65/IE1 
      fusion protein, previously shown to induce robust antibody and cellular immune 
      responses in mice, in a randomized, double-blind Phase 1 clinical trial in CMV 
      seronegative subjects. Forty subjects received a lower dose (LD) or higher dose 
      (HD) of vaccine or placebo by intramuscular or subcutaneous injection at Weeks 0, 
      8 and 24. The vaccine was well tolerated, with mild to moderate local 
      reactogenicity, minimal systemic reactogenicity, and no clinically important 
      changes in laboratory parameters. All vaccine recipients developed ex vivo, 
      direct IFN-gamma ELISPOT responses to CMV antigens (maximal mean spot-forming 
      cells per 10(6) PBMC in LD and HD groups of 348 and 504 for pp65, 83 and 113 for 
      IE1, and 138 and 114 for gB), and neutralizing antibodies (maximal geometric mean 
      titer 110 with LD and 218 with HD). Polyfunctional CD4(+) and CD8(+) T cell 
      responses were detected by polychromatic flow cytometry. This alphavirus replicon 
      particle vaccine was safe and induced neutralizing antibody and multifunctional T 
      cell responses against three CMV antigens that are important targets for 
      protective immunity.
FAU - Bernstein, David I
AU  - Bernstein DI
AD  - Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 
      University of Cincinnati, Cincinnati, OH 44259, USA. David.Bernstein@cchmc.org
FAU - Reap, Elizabeth A
AU  - Reap EA
FAU - Katen, Kevin
AU  - Katen K
FAU - Watson, Aubrey
AU  - Watson A
FAU - Smith, Kaitlin
AU  - Smith K
FAU - Norberg, Pamela
AU  - Norberg P
FAU - Olmsted, Robert A
AU  - Olmsted RA
FAU - Hoeper, Amy
AU  - Hoeper A
FAU - Morris, John
AU  - Morris J
FAU - Negri, Sarah
AU  - Negri S
FAU - Maughan, Maureen F
AU  - Maughan MF
FAU - Chulay, Jeffrey D
AU  - Chulay JD
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20091024
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antigens, Viral)
RN  - 0 (Cytomegalovirus Vaccines)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Neutralizing/immunology
MH  - Antibody Formation/immunology
MH  - Antigens, Viral/immunology
MH  - Cytomegalovirus/*immunology
MH  - Cytomegalovirus Vaccines/administration & dosage/adverse effects/*immunology
MH  - Double-Blind Method
MH  - Flow Cytometry
MH  - Humans
MH  - Immunity, Cellular/immunology
MH  - Middle Aged
MH  - Models, Biological
MH  - T-Lymphocytes/immunology
MH  - Young Adult
EDAT- 2009/10/28 06:00
MHDA- 2010/03/04 06:00
CRDT- 2009/10/28 06:00
PHST- 2009/07/16 00:00 [received]
PHST- 2009/09/21 00:00 [revised]
PHST- 2009/09/30 00:00 [accepted]
PHST- 2009/10/28 06:00 [entrez]
PHST- 2009/10/28 06:00 [pubmed]
PHST- 2010/03/04 06:00 [medline]
AID - S0264-410X(09)01495-9 [pii]
AID - 10.1016/j.vaccine.2009.09.135 [doi]
PST - ppublish
SO  - Vaccine. 2009 Dec 11;28(2):484-93. doi: 10.1016/j.vaccine.2009.09.135. Epub 2009 
      Oct 24.