PMID- 25045815
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20240130
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 32
IP  - 39
DP  - 2014 Sep 3
TI  - Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) 
      activity in a DNA prime-protein boost HIV-1 vaccine.
PG  - 5049-56
LID - S0264-410X(14)00936-0 [pii]
LID - 10.1016/j.vaccine.2014.07.010 [doi]
AB  - Recombinant protein vaccines are commonly formulated with an immune-stimulatory 
      compound, or adjuvant, to boost immune responses to a particular antigen. Recent 
      studies have shown that, through recognition of molecular motifs, receptors of 
      the innate immune system are involved in the functions of adjuvants to generate 
      and direct adaptive immune responses. However, it is not clear to which degree 
      those receptors are also important when the adjuvant is used as part of a novel 
      heterologous prime-boost immunization process in which the priming and boosting 
      components are not the same type of vaccines. In the current study, we compared 
      the immune responses elicited by a pentavalent HIV-1 DNA prime-protein boost 
      vaccine in mice deficient in either Toll-like receptor 4 (TLR4) or myeloid 
      differentiation primary response gene 88 (MyD88) to wildtype mice. HIV gp120 
      protein administered in the boost phase was formulated with either monophosphoryl 
      lipid A (MPLA), QS-21, or Al(OH)3. Endpoint antibody titer, serum cytokine 
      response and T-cell memory response were assessed. Neither TLR4 nor MyD88 
      deficiency had a significant effect on the immune response of mice given vaccine 
      formulated with QS-21 or Al(OH)3. However, TLR4- and MyD88-deficiency decreased 
      both the antibody and T-cell responses in mice administered HIV gp120 formulated 
      with MPLA. These results further our understanding of the activation of TLR4 and 
      MyD88 by MPLA in the context of a DNA prime/protein boost immunization strategy.
CI  - Copyright (c) 2014. Published by Elsevier Ltd.
FAU - Pouliot, Kimberly
AU  - Pouliot K
AD  - Division of Infectious Diseases and Immunology, Program in Innate Immunity, 
      Worcester, MA 01605, United States.
FAU - Buglione-Corbett, Rachel
AU  - Buglione-Corbett R
AD  - Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of 
      Massachusetts Medical School, Worcester, MA 01605, United States.
FAU - Marty-Roix, Robyn
AU  - Marty-Roix R
AD  - Division of Infectious Diseases and Immunology, Program in Innate Immunity, 
      Worcester, MA 01605, United States.
FAU - Montminy-Paquette, Sara
AU  - Montminy-Paquette S
AD  - Division of Infectious Diseases and Immunology, Program in Innate Immunity, 
      Worcester, MA 01605, United States.
FAU - West, Kim
AU  - West K
AD  - Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of 
      Massachusetts Medical School, Worcester, MA 01605, United States.
FAU - Wang, Shixia
AU  - Wang S
AD  - Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of 
      Massachusetts Medical School, Worcester, MA 01605, United States.
FAU - Lu, Shan
AU  - Lu S
AD  - Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of 
      Massachusetts Medical School, Worcester, MA 01605, United States.
FAU - Lien, Egil
AU  - Lien E
AD  - Division of Infectious Diseases and Immunology, Program in Innate Immunity, 
      Worcester, MA 01605, United States; Centre of Molecular Inflammation Research, 
      Dept. of Cancer and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic 
      address: egil.lien@umassmed.edu.
LA  - eng
GR  - U19 AI082676/AI/NIAID NIH HHS/United States
GR  - 5 P01 AI082274/AI/NIAID NIH HHS/United States
GR  - P01 AI082274/AI/NIAID NIH HHS/United States
GR  - 5 U19 AI082676/AI/NIAID NIH HHS/United States
GR  - R01 AI075318/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140718
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (AIDS Vaccines)
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cytokines)
RN  - 0 (HIV Antibodies)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipid A)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Saponins)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Vaccines, DNA)
RN  - 0 (gp120 protein, Human immunodeficiency virus 1)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
RN  - 61H83WZX3U (saponin QA-21V1)
RN  - MWC0ET1L2P (monophosphoryl lipid A)
SB  - IM
MH  - AIDS Vaccines/*immunology
MH  - Adjuvants, Immunologic/*administration & dosage
MH  - Aluminum Hydroxide/administration & dosage
MH  - Animals
MH  - Cytokines/immunology
MH  - HIV Antibodies/blood
MH  - HIV Envelope Protein gp120/immunology
MH  - HIV-1
MH  - Immunization, Secondary
MH  - Immunoglobulin G/blood
MH  - Immunologic Memory
MH  - Lipid A/administration & dosage/*analogs & derivatives
MH  - Mice
MH  - Myeloid Differentiation Factor 88/*immunology
MH  - Saponins/administration & dosage
MH  - T-Lymphocytes/immunology
MH  - Toll-Like Receptor 4/*immunology
MH  - Vaccines, DNA/immunology
PMC - PMC10687719
MID - NIHMS1026483
OTO - NOTNLM
OT  - Antibody response
OT  - DNA Prime-protein boost vaccine
OT  - MPLA
OT  - MyD88
OT  - TLR4
COIS- Conflict of interest statement The authors declare no conflicts of interest.
EDAT- 2014/07/22 06:00
MHDA- 2015/03/31 06:00
PMCR- 2023/11/30
CRDT- 2014/07/22 06:00
PHST- 2014/01/16 00:00 [received]
PHST- 2014/06/17 00:00 [revised]
PHST- 2014/07/08 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2023/11/30 00:00 [pmc-release]
AID - S0264-410X(14)00936-0 [pii]
AID - 10.1016/j.vaccine.2014.07.010 [doi]
PST - ppublish
SO  - Vaccine. 2014 Sep 3;32(39):5049-56. doi: 10.1016/j.vaccine.2014.07.010. Epub 2014 
      Jul 18.