PMID- 34248966
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20220310
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation 
      Using a Design of Experiments Strategy.
PG  - 683157
LID - 10.3389/fimmu.2021.683157 [doi]
LID - 683157
AB  - Amebiasis is a neglected tropical disease caused by Entamoeba histolytica. 
      Although the disease burden varies geographically, amebiasis is estimated to 
      account for some 55,000 deaths and millions of infections globally per year. 
      Children and travelers are among the groups with the greatest risk of infection. 
      There are currently no licensed vaccines for prevention of amebiasis, although 
      key immune correlates for protection have been proposed from observational 
      studies in humans. We previously described the development of a liposomal 
      adjuvant formulation containing two synthetic TLR ligands (GLA and 3M-052) that 
      enhanced antigen-specific fecal IgA, serum IgG2a, a mixed IFNgamma and IL-17A 
      cytokine profile from splenocytes, and protective efficacy following intranasal 
      administration with the LecA antigen. By applying a statistical design of 
      experiments (DOE) and desirability function approach, we now describe the 
      optimization of the dose of each vaccine formulation component (LecA, GLA, 
      3M-052, and liposome) as well as the excipient composition (acyl chain length and 
      saturation; PEGylated lipid:phospholipid ratio; and presence of antioxidant, 
      tonicity, or viscosity agents) to maximize desired immunogenicity characteristics 
      while maintaining physicochemical stability. This DOE/desirability index approach 
      led to the identification of a lead candidate composition that demonstrated 
      immune response durability and protective efficacy in the mouse model, as well as 
      an assessment of the impact of each active vaccine formulation component on 
      protection. Thus, we demonstrate that both GLA and 3M-052 are required for 
      statistically significant protective efficacy. We also show that immunogenicity 
      and efficacy results differ in female vs male mice, and the differences appear to 
      be at least partly associated with adjuvant formulation composition.
CI  - Copyright (c) 2021 Abhyankar, Orr, Kinsey, Sivananthan, Nafziger, Oakland, Young, 
      Farr, Uddin, Leslie, Burgess, Liang, De Lima, Larson, Guderian, Lin, Kahn, Ghosh, 
      Reed, Tomai, Pedersen, Petri and Fox.
FAU - Abhyankar, Mayuresh M
AU  - Abhyankar MM
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Orr, Mark T
AU  - Orr MT
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
AD  - Department of Global Health, University of Washington, Seattle, WA, United 
      States.
FAU - Kinsey, Robert
AU  - Kinsey R
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Sivananthan, Sandra
AU  - Sivananthan S
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Nafziger, Andrew J
AU  - Nafziger AJ
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Oakland, David N
AU  - Oakland DN
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Young, Mary K
AU  - Young MK
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Farr, Laura
AU  - Farr L
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Uddin, Md Jashim
AU  - Uddin MJ
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Leslie, Jhansi L
AU  - Leslie JL
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Burgess, Stacey L
AU  - Burgess SL
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Liang, Hong
AU  - Liang H
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - De Lima, Ines
AU  - De Lima I
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Larson, Elise
AU  - Larson E
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Guderian, Jeffrey A
AU  - Guderian JA
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Lin, Susan
AU  - Lin S
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Kahn, Aaron
AU  - Kahn A
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Ghosh, Prakash
AU  - Ghosh P
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Reed, Sierra
AU  - Reed S
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
FAU - Tomai, Mark A
AU  - Tomai MA
AD  - 3M Corporate Research Materials Laboratory, 3M Center, St Paul, MN, United 
      States.
FAU - Pedersen, Karl
AU  - Pedersen K
AD  - TECHLAB, Inc., Blacksburg, VA, United States.
FAU - Petri, William A Jr
AU  - Petri WA Jr
AD  - Division of Infectious Diseases and International Health, Department of Medicine, 
      University of Virginia Health System, Charlottesville, VA, United States.
FAU - Fox, Christopher B
AU  - Fox CB
AD  - Infectious Disease Research Institute (IDRI), Seattle, WA, United States.
AD  - Department of Global Health, University of Washington, Seattle, WA, United 
      States.
LA  - eng
GR  - R01 AI146257/AI/NIAID NIH HHS/United States
GR  - T32 AI007496/AI/NIAID NIH HHS/United States
GR  - HHSN272201800025C/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210625
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Liposomes)
RN  - 0 (Protozoan Vaccines)
SB  - IM
MH  - Adjuvants, Immunologic/chemistry
MH  - Administration, Intranasal
MH  - Animals
MH  - Antibodies, Protozoan/blood/immunology
MH  - Antigens, Protozoan/*immunology
MH  - Chemical Phenomena
MH  - Cytokines/metabolism
MH  - Drug Compounding
MH  - Entamoeba histolytica/*immunology
MH  - Entamoebiasis/*immunology/parasitology/*prevention & control
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Immunogenicity, Vaccine
MH  - Immunoglobulin G/immunology
MH  - Liposomes
MH  - Mice
MH  - Protozoan Vaccines/administration & dosage/chemistry/*immunology
MH  - Vaccination
PMC - PMC8268010
OTO - NOTNLM
OT  - Entamoeba histolytica
OT  - TLR ligand
OT  - design of experiments
OT  - formulation
OT  - intranasal
OT  - liposome
OT  - vaccine adjuvant
COIS- MT is an employee of 3M and 3M-052 is an asset of 3M's. WP is a consultant for 
      TechLab, Inc. and in addition receives royalties for amebiasis diagnostics that 
      are donated in their entirety to the American Society of Tropical Medicine and 
      Hygiene. KP is an employee of TechLab, Inc. and amebiasis diagnostics are an 
      asset of TechLab's. CF, RK, SS, HL, IL, EL, JG, SL, AK, and SR are employees of 
      IDRI, which owns assets including patents and patent applications involving 
      formulations of GLA and 3M-052 including what is represented in this article. MA, 
      WP, CF, and SL are inventors on patent/patent application(s) involving the 
      vaccine formulations represented in this article. The remaining authors declare 
      that the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2021/07/13 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/06/25
CRDT- 2021/07/12 05:48
PHST- 2021/03/20 00:00 [received]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/07/12 05:48 [entrez]
PHST- 2021/07/13 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/06/25 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.683157 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jun 25;12:683157. doi: 10.3389/fimmu.2021.683157. eCollection 
      2021.