PMID- 28077440
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20210409
IS  - 1556-679X (Electronic)
IS  - 1556-6811 (Print)
IS  - 1556-679X (Linking)
VI  - 24
IP  - 3
DP  - 2017 Mar
TI  - Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis 
      LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 
      Challenge by Augmenting both Humoral and Cellular Immunity.
LID - 10.1128/CVI.00574-16 [doi]
LID - e00574-16
AB  - Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in 
      the United States. Previously, we showed that incorporating lysates from 
      partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 
      strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu 
      S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal 
      (i.p.) challenge in mice. However, we achieved only partial protection against F. 
      tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous 
      prime-boost immunization strategies. We now extend these findings to show that 
      both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers 
      of anti-F. tularensis IgG and that the titers could be further increased by 
      adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) 
      adjuvant that is included in several U.S. FDA-approved vaccines. LVS-V+MPL immune 
      sera also detected more F. tularensis antigens than LVS-V immune sera and, after 
      passive transfer to naive mice, significantly delayed the time to death against 
      F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active 
      immunization with LVS-V+MPL (i.p./i.p.) also increased the frequency of gamma 
      interferon (IFN-gamma)-secreting activated helper T cells, IFN-gamma production, and the 
      ability of splenocytes to control intramacrophage F. tularensis LVS replication 
      ex vivo Active LVS-V+MPL immunization via heterologous routes (i.p./i.n.) 
      significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and 
      significantly enhanced protection against i.n. F. tularensis Schu S4 challenge 
      (to  approximately 60%). These data represent a significant step in the development of a 
      subunit vaccine against the highly virulent type A strains.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Richard, Katharina
AU  - Richard K
AD  - Department of Microbiology and Immunology, University of Maryland School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Mann, Barbara J
AU  - Mann BJ
AD  - Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
FAU - Qin, Aiping
AU  - Qin A
AD  - Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
FAU - Barry, Eileen M
AU  - Barry EM
AD  - Center for Vaccine Development, University of Maryland School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Ernst, Robert K
AU  - Ernst RK
AD  - Department of Microbial Pathogenesis, University of Maryland School of Dentistry, 
      Baltimore, Maryland, USA.
FAU - Vogel, Stefanie N
AU  - Vogel SN
AD  - Department of Microbiology and Immunology, University of Maryland School of 
      Medicine, Baltimore, Maryland, USA svogel@som.umaryland.edu.
LA  - eng
GR  - R01 AI102966/AI/NIAID NIH HHS/United States
GR  - R01 AI123129/AI/NIAID NIH HHS/United States
GR  - R21 AI101691/AI/NIAID NIH HHS/United States
GR  - R56 AI018797/AI/NIAID NIH HHS/United States
GR  - T32 AI095190/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170306
PL  - United States
TA  - Clin Vaccine Immunol
JT  - Clinical and vaccine immunology : CVI
JID - 101252125
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lipid A)
RN  - 0 (Vaccines, Subunit)
RN  - 82115-62-6 (Interferon-gamma)
RN  - MWC0ET1L2P (monophosphoryl lipid A)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage
MH  - Animals
MH  - Antibodies, Bacterial/blood
MH  - Bacterial Vaccines/administration & dosage/*immunology
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Disease Models, Animal
MH  - Female
MH  - Francisella tularensis/*immunology
MH  - *Immunity, Cellular
MH  - *Immunity, Humoral
MH  - Immunoglobulin A/analysis
MH  - Immunoglobulin G/analysis
MH  - Interferon-gamma/metabolism
MH  - Lipid A/administration & dosage/*analogs & derivatives
MH  - Macrophages/immunology
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/administration & dosage
MH  - Survival Analysis
MH  - T-Lymphocytes/immunology
MH  - Tularemia/immunology/*prevention & control
MH  - Vaccines, Subunit/administration & dosage/immunology
PMC - PMC5339645
OTO - NOTNLM
OT  - Francisella tularensis
OT  - LVS
OT  - Schu S4
OT  - catanionic surfactant
OT  - immunization
OT  - mice
OT  - monophosphoryl lipid A
OT  - nanoparticle
OT  - subunit vaccine
OT  - tularemia
EDAT- 2017/01/13 06:00
MHDA- 2017/09/02 06:00
PMCR- 2017/09/06
CRDT- 2017/01/13 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/01/06 00:00 [accepted]
PHST- 2017/01/13 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2017/01/13 06:00 [entrez]
PHST- 2017/09/06 00:00 [pmc-release]
AID - CVI.00574-16 [pii]
AID - 00574-16 [pii]
AID - 10.1128/CVI.00574-16 [doi]
PST - epublish
SO  - Clin Vaccine Immunol. 2017 Mar 6;24(3):e00574-16. doi: 10.1128/CVI.00574-16. 
      Print 2017 Mar.