PMID- 20097152
OWN - NLM
STAT- MEDLINE
DA  - 20100312
DCOM- 20100525
LR  - 20130531
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 28
IP  - 15
DP  - 2010 Mar 24
TI  - Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and
      efficacy studies in mice and monkeys.
PG  - 2705-15
LID - 10.1016/j.vaccine.2010.01.022 [doi]
AB  - Truncated recombinant dengue virus envelope protein subunits (80E) are
      efficiently expressed using the Drosophila Schneider-2 (S2) cell expression
      system. Binding of conformationally sensitive antibodies as well as X-ray crystal
      structural studies indicate that the recombinant 80E subunits are properly folded
      native-like proteins. Combining the 80E subunits from each of the four dengue
      serotypes with ISCOMATRIX adjuvant, an adjuvant selected from a set of adjuvants 
      tested for maximal and long lasting immune responses, results in high titer virus
      neutralizing antibody responses. Immunization of mice with a mixture of all four 
      80E subunits and ISCOMATRIX adjuvant resulted in potent virus neutralizing
      antibody responses to each of the four serotypes. The responses to the components
      of the tetravalent mixture were equivalent to the responses to each of the
      subunits administered individually. In an effort to evaluate the potential
      protective efficacy of the Drosophila expressed 80E, the dengue serotype 2
      (DEN2-80E) subunit was tested in both the mouse and monkey challenge models. In
      both models protection against viral challenge was achieved with low doses of
      antigen in the vaccine formulation. In non-human primates, low doses of the
      tetravalent formulation induced good virus neutralizing antibody titers to all
      four serotypes and protection against challenge with the two dengue virus
      serotypes tested. In contrast to previous reports, where subunit vaccine
      candidates have generally failed to induce potent, protective responses,
      native-like soluble 80E proteins expressed in the Drosophila S2 cells and
      administered with appropriate adjuvants are highly immunogenic and capable of
      eliciting protective responses in both mice and monkeys. These results support
      the development of a dengue virus tetravalent vaccine based on the four 80E
      subunits produced in the Drosophila S2 cell expression system.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
AD  - Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Aiea, HI 96701, United States.
FAU - Clements, David E
AU  - Clements DE
FAU - Coller, Beth-Ann G
AU  - Coller BA
FAU - Lieberman, Michael M
AU  - Lieberman MM
FAU - Ogata, Steven
AU  - Ogata S
FAU - Wang, Gordon
AU  - Wang G
FAU - Harada, Kent E
AU  - Harada KE
FAU - Putnak, J Robert
AU  - Putnak JR
FAU - Ivy, John M
AU  - Ivy JM
FAU - McDonell, Michael
AU  - McDonell M
FAU - Bignami, Gary S
AU  - Bignami GS
FAU - Peters, Iain D
AU  - Peters ID
FAU - Leung, Julia
AU  - Leung J
FAU - Weeks-Levy, Carolyn
AU  - Weeks-Levy C
FAU - Nakano, Eileen T
AU  - Nakano ET
FAU - Humphreys, Tom
AU  - Humphreys T
LA  - eng
GR  - 1 R43AI35401/AI/NIAID NIH HHS/United States
GR  - 2 R44AI35401/AI/NIAID NIH HHS/United States
GR  - R44 AI035401-02A1/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20100122
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Dengue Vaccines)
RN  - 0 (Drug Combinations)
RN  - 0 (ISCOMATRIX)
RN  - 0 (Phospholipids)
RN  - 0 (Saponins)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (Viral Envelope Proteins)
RN  - 57-88-5 (Cholesterol)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Animals
MH  - Antibodies, Neutralizing/*blood
MH  - Antibodies, Viral/*blood
MH  - Cell Line
MH  - Cholesterol/administration & dosage
MH  - Crystallography, X-Ray
MH  - Dengue/*prevention & control
MH  - Dengue Vaccines/*immunology
MH  - Dengue Virus/chemistry/genetics/*immunology
MH  - Disease Models, Animal
MH  - Drosophila
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Macaca mulatta
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phospholipids/administration & dosage
MH  - Protein Folding
MH  - Protein Structure, Tertiary
MH  - Saponins/administration & dosage
MH  - Vaccines, Subunit/immunology
MH  - Vaccines, Synthetic/immunology
MH  - Viral Envelope Proteins/chemistry/genetics/*immunology
PMC - PMC2837772
MID - NIHMS171542
OID - NLM: NIHMS171542
OID - NLM: PMC2837772
EDAT- 2010/01/26 06:00
MHDA- 2010/05/26 06:00
CRDT- 2010/01/26 06:00
PHST- 2009/09/03 [received]
PHST- 2009/12/08 [revised]
PHST- 2010/01/13 [accepted]
PHST- 2010/01/22 [aheadofprint]
AID - S0264-410X(10)00054-X [pii]
AID - 10.1016/j.vaccine.2010.01.022 [doi]
PST - ppublish
SO  - Vaccine. 2010 Mar 24;28(15):2705-15. doi: 10.1016/j.vaccine.2010.01.022. Epub
      2010 Jan 22.