PMID- 21389121
OWN - NLM
STAT- MEDLINE
DCOM- 20110620
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 10
DP  - 2011 May
TI  - Development of a glycoprotein D-expressing dominant-negative and 
      replication-defective herpes simplex virus 2 (HSV-2) recombinant viral vaccine 
      against HSV-2 infection in mice.
PG  - 5036-47
LID - 10.1128/JVI.02548-10 [doi]
AB  - Using the T-REx (Invitrogen, California) gene switch technology and a 
      dominant-negative mutant polypeptide of herpes simplex virus 1 (HSV-1)-origin 
      binding protein UL9, we previously constructed a glycoprotein D-expressing 
      replication-defective and dominant-negative HSV-1 recombinant viral vaccine, 
      CJ9-gD, for protection against HSV infection and disease. It was demonstrated 
      that CJ9-gD is avirulent following intracerebral inoculation in mice, cannot 
      establish detectable latent infection following different routes of infection, 
      and offers highly effective protective immunity against primary HSV-1 and HSV-2 
      infection and disease in mouse and guinea pig models of HSV infections. Given 
      these favorable safety and immunological profiles of CJ9-gD, aiming to maximize 
      levels of HSV-2 glycoprotein D (gD2) expression, we have constructed an ICP0 null 
      mutant-based dominant-negative and replication-defective HSV-2 recombinant, 
      CJ2-gD2, that contains 2 copies of the gD2 gene driven by the tetracycline 
      operator (tetO)-bearing HSV-1 major immediate-early ICP4 promoter. CJ2-gD2 
      expresses gD2 as efficiently as wild-type HSV-2 infection and can lead to a 
      150-fold reduction in wild-type HSV-2 viral replication in cells coinfected with 
      CJ2-gD2 and wild-type HSV-2 at the same multiplicity of infection. CJ2-gD2 is 
      avirulent following intracerebral injection and cannot establish a detectable 
      latent infection following subcutaneous (s.c.) immunization. CJ2-gD2 is a more 
      effective vaccine than HSV-1 CJ9-gD and a non-gD2-expressing dominant-negative 
      and replication-defective HSV-2 recombinant in protection against wild-type HSV-2 
      genital disease. Using recall response, we showed that immunization with CJ2-gD2 
      elicited strong HSV-2-specific memory CD4(+) and CD8(+) T-cell responses. 
      Collectively, given the demonstrated preclinical immunogenicity and its unique 
      safety profiles, CJ2-gD2 represents a new class of HSV-2 replication-defective 
      recombinant viral vaccines in protection against HSV-2 genital infection and 
      disease.
FAU - Akhrameyeva, Natalie V
AU  - Akhrameyeva NV
AD  - Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 
      Francis Street, Boston, MA 02115, USA.
FAU - Zhang, Pengwei
AU  - Zhang P
FAU - Sugiyama, Nao
AU  - Sugiyama N
FAU - Behar, Samuel M
AU  - Behar SM
FAU - Yao, Feng
AU  - Yao F
LA  - eng
GR  - 5R01AI05088/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110309
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Viral Vaccines)
RN  - 0 (glycoprotein D-herpes simplex virus type 2)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - *Gene Expression
MH  - Herpes Simplex/immunology/*prevention & control
MH  - Herpesvirus 2, Human/genetics/*immunology/*pathogenicity
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Viral Envelope Proteins/*genetics
MH  - Viral Vaccines/administration & dosage/genetics/*immunology
PMC - PMC3126160
EDAT- 2011/03/11 06:00
MHDA- 2011/06/21 06:00
PMCR- 2011/11/01
CRDT- 2011/03/11 06:00
PHST- 2011/03/11 06:00 [entrez]
PHST- 2011/03/11 06:00 [pubmed]
PHST- 2011/06/21 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - JVI.02548-10 [pii]
AID - 2548-10 [pii]
AID - 10.1128/JVI.02548-10 [doi]
PST - ppublish
SO  - J Virol. 2011 May;85(10):5036-47. doi: 10.1128/JVI.02548-10. Epub 2011 Mar 9.