PMID- 30250170
OWN - NLM
STAT- MEDLINE
DCOM- 20190115
LR  - 20240313
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Sep 24
TI  - Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV 
      infections in vivo.
PG  - 3881
LID - 10.1038/s41467-018-06349-0 [doi]
LID - 3881
AB  - Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies 
      with proven in vivo efficacy rely on antiretroviral drugs, creating the potential 
      for drug resistance and complicated treatment options in individuals who become 
      infected. Moreover, on-demand products are currently missing from the PrEP 
      development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry 
      inhibitor derived from red algae with an excellent safety profile and potent 
      activity in vitro. When combined with carrageenan (CG), GRFT has strong activity 
      against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro 
      and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving 
      insert (FDI) formulation for on-demand use protects rhesus macaques from a high 
      dose vaginal SHIV SF162P3 challenge 4 h after FDI insertion. Furthermore, the 
      GRFT/CG FDI also protects mice vaginally against HSV-2 and HPV pseudovirus. As a 
      safe, potent, broad-spectrum, on-demand non-antiretroviral product, the GRFT/CG 
      FDI warrants clinical development.
FAU - Derby, Nina
AU  - Derby N
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA. nderby@popcouncil.org.
FAU - Lal, Manjari
AU  - Lal M
AD  - PATH, 2201 Westlake Ave, Suite 200, Seattle, WA, 98121, USA.
FAU - Aravantinou, Meropi
AU  - Aravantinou M
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Kizima, Larisa
AU  - Kizima L
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Barnable, Patrick
AU  - Barnable P
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Rodriguez, Aixa
AU  - Rodriguez A
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Lai, Manshun
AU  - Lai M
AD  - PATH, 2201 Westlake Ave, Suite 200, Seattle, WA, 98121, USA.
FAU - Wesenberg, Asa
AU  - Wesenberg A
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Ugaonkar, Shweta
AU  - Ugaonkar S
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Levendosky, Keith
AU  - Levendosky K
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Mizenina, Olga
AU  - Mizenina O
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Kleinbeck, Kyle
AU  - Kleinbeck K
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Lifson, Jeffrey D
AU  - Lifson JD
AD  - AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, 8560 Progress Dr, Frederick, MD, 21701, 
      USA.
FAU - Peet, M Melissa
AU  - Peet MM
AD  - MPI Research, 54943 N. Main St, Mattawan, MI, 49071, USA.
FAU - Lloyd, Zachary
AU  - Lloyd Z
AD  - MPI Research, 54943 N. Main St, Mattawan, MI, 49071, USA.
FAU - Benson, Michael
AU  - Benson M
AD  - MPI Research, 54943 N. Main St, Mattawan, MI, 49071, USA.
FAU - Heneine, Walid
AU  - Heneine W
AD  - Centers for Disease Control, 1600 Clifton Rd, Atlanta, GA, 30333, USA.
FAU - O'Keefe, Barry R
AU  - O'Keefe BR
AUID- ORCID: 0000-0003-0772-4856
AD  - Molecular Targets Program, Center for Cancer Research, and Natural Products 
      Branch, Developmental Therapeutics Program, Division of Cancer Treatment and 
      Diagnosis, National Cancer Institute, Building 560, Room 21-105, Frederick, MD, 
      21702-1201, USA.
FAU - Robbiani, Melissa
AU  - Robbiani M
AD  - MJR4CONSULTING, New York, 10065, NY, USA.
FAU - Martinelli, Elena
AU  - Martinelli E
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Grasperge, Brooke
AU  - Grasperge B
AD  - Tulane National Primate Research Center, 18703 Three Rivers Rd, Covington, LA, 
      70433-8915, USA.
FAU - Blanchard, James
AU  - Blanchard J
AD  - Tulane National Primate Research Center, 18703 Three Rivers Rd, Covington, LA, 
      70433-8915, USA.
FAU - Gettie, Agegnehu
AU  - Gettie A
AD  - Aaron Diamond AIDS Research Center, 455 1st Ave. #7, New York, NY, 10016, USA.
FAU - Teleshova, Natalia
AU  - Teleshova N
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
FAU - Fernandez-Romero, Jose A
AU  - Fernandez-Romero JA
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
AD  - Science Department, Borough of Manhattan Community College, 199 Chambers St, New 
      York, NY, 10007, USA.
FAU - Zydowsky, Thomas M
AU  - Zydowsky TM
AD  - Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 
      10065, USA.
LA  - eng
GR  - P51 OD011104/OD/NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180924
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Antiviral Agents)
RN  - 0 (Plant Lectins)
RN  - 9000-07-1 (Carrageenan)
RN  - Z8PX5UX50U (griffithsin protein, Griffithsia)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*prevention & control
MH  - Administration, Intravaginal
MH  - Animals
MH  - Antiviral Agents/chemistry/*therapeutic use
MH  - Carrageenan/chemistry/*therapeutic use
MH  - Disease Models, Animal
MH  - Drug Compounding/methods
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Freeze Drying
MH  - Herpes Genitalis/*prevention & control/virology
MH  - Herpesvirus 2, Human/pathogenicity
MH  - Humans
MH  - Macaca mulatta
MH  - Male
MH  - Papillomavirus Infections/*prevention & control/virology
MH  - Plant Lectins/chemistry/genetics/isolation & purification/*therapeutic use
MH  - Plants, Genetically Modified/genetics/metabolism
MH  - Pre-Exposure Prophylaxis/methods
MH  - Simian Acquired Immunodeficiency Syndrome/prevention & control
MH  - Simian Immunodeficiency Virus/pathogenicity
MH  - Nicotiana/genetics/metabolism
MH  - Treatment Outcome
MH  - Vagina/virology
PMC - PMC6155161
COIS- The authors declare no competing interests.
EDAT- 2018/09/27 06:00
MHDA- 2019/01/16 06:00
PMCR- 2018/09/24
CRDT- 2018/09/26 06:00
PHST- 2018/04/13 00:00 [received]
PHST- 2018/08/24 00:00 [accepted]
PHST- 2018/09/26 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2019/01/16 06:00 [medline]
PHST- 2018/09/24 00:00 [pmc-release]
AID - 10.1038/s41467-018-06349-0 [pii]
AID - 6349 [pii]
AID - 10.1038/s41467-018-06349-0 [doi]
PST - epublish
SO  - Nat Commun. 2018 Sep 24;9(1):3881. doi: 10.1038/s41467-018-06349-0.