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Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy

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 i...

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Autores principales: Abhyankar, Mayuresh M., Orr, Mark T., Kinsey, Robert, Sivananthan, Sandra, Nafziger, Andrew J., Oakland, David N., Young, Mary K., Farr, Laura, Uddin, Md Jashim, Leslie, Jhansi L., Burgess, Stacey L., Liang, Hong, De Lima, Ines, Larson, Elise, Guderian, Jeffrey A., Lin, Susan, Kahn, Aaron, Ghosh, Prakash, Reed, Sierra, Tomai, Mark A., Pedersen, Karl, Petri, William A., Fox, Christopher B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268010/
https://www.ncbi.nlm.nih.gov/pubmed/34248966
http://dx.doi.org/10.3389/fimmu.2021.683157
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author Abhyankar, Mayuresh M.
Orr, Mark T.
Kinsey, Robert
Sivananthan, Sandra
Nafziger, Andrew J.
Oakland, David N.
Young, Mary K.
Farr, Laura
Uddin, Md Jashim
Leslie, Jhansi L.
Burgess, Stacey L.
Liang, Hong
De Lima, Ines
Larson, Elise
Guderian, Jeffrey A.
Lin, Susan
Kahn, Aaron
Ghosh, Prakash
Reed, Sierra
Tomai, Mark A.
Pedersen, Karl
Petri, William A.
Fox, Christopher B.
author_facet Abhyankar, Mayuresh M.
Orr, Mark T.
Kinsey, Robert
Sivananthan, Sandra
Nafziger, Andrew J.
Oakland, David N.
Young, Mary K.
Farr, Laura
Uddin, Md Jashim
Leslie, Jhansi L.
Burgess, Stacey L.
Liang, Hong
De Lima, Ines
Larson, Elise
Guderian, Jeffrey A.
Lin, Susan
Kahn, Aaron
Ghosh, Prakash
Reed, Sierra
Tomai, Mark A.
Pedersen, Karl
Petri, William A.
Fox, Christopher B.
author_sort Abhyankar, Mayuresh M.
collection PubMed
description 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 IFNγ 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.
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spelling pubmed-82680102021-07-10 Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy Abhyankar, Mayuresh M. Orr, Mark T. Kinsey, Robert Sivananthan, Sandra Nafziger, Andrew J. Oakland, David N. Young, Mary K. Farr, Laura Uddin, Md Jashim Leslie, Jhansi L. Burgess, Stacey L. Liang, Hong De Lima, Ines Larson, Elise Guderian, Jeffrey A. Lin, Susan Kahn, Aaron Ghosh, Prakash Reed, Sierra Tomai, Mark A. Pedersen, Karl Petri, William A. Fox, Christopher B. Front Immunol Immunology 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 IFNγ 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. Frontiers Media S.A. 2021-06-25 /pmc/articles/PMC8268010/ /pubmed/34248966 http://dx.doi.org/10.3389/fimmu.2021.683157 Text en Copyright © 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 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Abhyankar, Mayuresh M.
Orr, Mark T.
Kinsey, Robert
Sivananthan, Sandra
Nafziger, Andrew J.
Oakland, David N.
Young, Mary K.
Farr, Laura
Uddin, Md Jashim
Leslie, Jhansi L.
Burgess, Stacey L.
Liang, Hong
De Lima, Ines
Larson, Elise
Guderian, Jeffrey A.
Lin, Susan
Kahn, Aaron
Ghosh, Prakash
Reed, Sierra
Tomai, Mark A.
Pedersen, Karl
Petri, William A.
Fox, Christopher B.
Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title_full Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title_fullStr Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title_full_unstemmed Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title_short Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy
title_sort optimizing a multi-component intranasal entamoeba histolytica vaccine formulation using a design of experiments strategy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268010/
https://www.ncbi.nlm.nih.gov/pubmed/34248966
http://dx.doi.org/10.3389/fimmu.2021.683157
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