PMID- 27536733
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230726
IS  - 2379-3708 (Print)
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 1
IP  - 12
DP  - 2016 Aug 4
TI  - HSV-2 DeltagD elicits FcgammaR-effector antibodies that protect against clinical 
      isolates.
LID - e88529 [pii]
AB  - A single-cycle herpes simplex virus (HSV) deleted in glycoprotein D (DeltagD-2) 
      elicited high titer HSV-specific antibodies (Abs) that (i) were rapidly 
      transported into the vaginal mucosa; (ii) elicited antibody-dependent 
      cell-mediated cytotoxicity but little neutralization; (iii) provided complete 
      protection against lethal intravaginal challenge; and (iv) prevented 
      establishment of latency in mice. However, clinical isolates may differ 
      antigenically and impact vaccine efficacy. To determine the breadth and further 
      define mechanisms of protection of this vaccine candidate, we tested DeltagD-2 
      against a panel of clinical isolates in a murine skin challenge model. The 
      isolates were genetically diverse, as evidenced by genomic sequencing and in vivo 
      virulence. Prime and boost immunization (s.c.) with live but not heat- or 
      UV-inactivated DeltagD-2 completely protected mice from challenge with the most 
      virulent HSV-1 and HSV-2 isolates. Furthermore, mice were completely protected 
      against 100 times the lethal dose that typically kills 90% of animals (LD90) of a 
      South African isolate (SD90), and no latent virus was detected in dorsal root 
      ganglia. Immunization was associated with rapid recruitment of HSV-specific 
      FcgammaRIII- and FcgammaRIV-activating IgG2 Abs into the skin, resolution of local 
      cytokine and cellular inflammatory responses, and viral clearance by day 5 after 
      challenge. Rapid clearance and the absence of latent virus suggest that DeltagD-2 
      elicits sterilizing immunity.
FAU - Petro, Christopher D
AU  - Petro CD
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York, USA; Howard Hughes Medical Institute, Albert Einstein College of 
      Medicine, Bronx, New York, USA; Department of Pediatrics, Albert Einstein College 
      of Medicine, Bronx, New York, USA.
FAU - Weinrick, Brian
AU  - Weinrick B
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York, USA; Howard Hughes Medical Institute, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Khajoueinejad, Nazanin
AU  - Khajoueinejad N
AD  - Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Burn, Clare
AU  - Burn C
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York, USA; Department of Pediatrics, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Sellers, Rani
AU  - Sellers R
AD  - Histology and Comparative Pathology Facility, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Jacobs, William R Jr
AU  - Jacobs WR Jr
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York, USA; Howard Hughes Medical Institute, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Herold, Betsy C
AU  - Herold BC
AD  - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 
      Bronx, New York, USA; Department of Pediatrics, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
LA  - eng
GR  - R01 AI117321/AI/NIAID NIH HHS/United States
GR  - R37 AI026170/AI/NIAID NIH HHS/United States
GR  - R01 AI026170/AI/NIAID NIH HHS/United States
GR  - R01 AI065309/AI/NIAID NIH HHS/United States
GR  - R01 AI098925/AI/NIAID NIH HHS/United States
GR  - U19 AI103461/AI/NIAID NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
PMC - PMC4985247
MID - NIHMS808466
EDAT- 2016/08/19 06:00
MHDA- 2016/08/19 06:01
PMCR- 2016/08/04
CRDT- 2016/08/19 06:00
PHST- 2016/08/19 06:01 [medline]
PHST- 2016/08/19 06:00 [entrez]
PHST- 2016/08/19 06:00 [pubmed]
PHST- 2016/08/04 00:00 [pmc-release]
AID - e88529 [pii]
AID - 88529 [pii]
AID - 10.1172/jci.insight.88529 [doi]
PST - ppublish
SO  - JCI Insight. 2016 Aug 4;1(12):e88529. doi: 10.1172/jci.insight.88529.