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Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles

Chlamydia trachomatis is a sexually transmitted bacterium that infects over 130 million individuals worldwide annually. To implement a vaccine, we developed a cell-free co-translational system to express the Chlamydia muridarum major outer membrane protein (MOMP). This approach uses a nanolipoprotei...

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Autores principales: Tifrea, Delia F., He, Wei, Pal, Sukumar, Evans, Angela C., Gilmore, Sean F., Fischer, Nicholas O., Rasley, Amy, Coleman, Matthew A., de la Maza, Luis M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310061/
https://www.ncbi.nlm.nih.gov/pubmed/34358171
http://dx.doi.org/10.3390/vaccines9070755
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author Tifrea, Delia F.
He, Wei
Pal, Sukumar
Evans, Angela C.
Gilmore, Sean F.
Fischer, Nicholas O.
Rasley, Amy
Coleman, Matthew A.
de la Maza, Luis M.
author_facet Tifrea, Delia F.
He, Wei
Pal, Sukumar
Evans, Angela C.
Gilmore, Sean F.
Fischer, Nicholas O.
Rasley, Amy
Coleman, Matthew A.
de la Maza, Luis M.
author_sort Tifrea, Delia F.
collection PubMed
description Chlamydia trachomatis is a sexually transmitted bacterium that infects over 130 million individuals worldwide annually. To implement a vaccine, we developed a cell-free co-translational system to express the Chlamydia muridarum major outer membrane protein (MOMP). This approach uses a nanolipoprotein particles (tNLP) made from ApoA1 protein, amphiphilic telodendrimer and lipids that self-assemble to form 10–25 nm discs. These tNLP provide a protein-encapsulated lipid support to solubilize and fold membrane proteins. The cell-free system co-translated MOMP and ApoA1 in the presence of telodendrimer mixed with lipids. The MOMP-tNLP complex was amenable to CpG and FSL-1 adjuvant addition. To investigate the ability of MOMP-tNLP+CpG+FSL-1 to induce protection against an intranasal (i.n.) C. muridarum challenge, female mice were vaccinated intramuscularly (i.m.) or i.n. and i.m. simultaneously 4 weeks apart. Following vaccination with MOMP-tNLP+CpG+FSL-1, mice mounted significant humoral and cell-mediated immune responses. Following the i.n. challenge, mice vaccinated with MOMP-tNLP+CpG+FSL-1 i.n. + i.m. group were protected as determined by the percentage change in body weight and by the number of C. muridarum inclusion forming units (IFU) recovered from the lungs. To our knowledge, this is the first time a MOMP-based vaccine formulated in tNLP has been shown to protect against C. muridarum.
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spelling pubmed-83100612021-07-25 Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles Tifrea, Delia F. He, Wei Pal, Sukumar Evans, Angela C. Gilmore, Sean F. Fischer, Nicholas O. Rasley, Amy Coleman, Matthew A. de la Maza, Luis M. Vaccines (Basel) Article Chlamydia trachomatis is a sexually transmitted bacterium that infects over 130 million individuals worldwide annually. To implement a vaccine, we developed a cell-free co-translational system to express the Chlamydia muridarum major outer membrane protein (MOMP). This approach uses a nanolipoprotein particles (tNLP) made from ApoA1 protein, amphiphilic telodendrimer and lipids that self-assemble to form 10–25 nm discs. These tNLP provide a protein-encapsulated lipid support to solubilize and fold membrane proteins. The cell-free system co-translated MOMP and ApoA1 in the presence of telodendrimer mixed with lipids. The MOMP-tNLP complex was amenable to CpG and FSL-1 adjuvant addition. To investigate the ability of MOMP-tNLP+CpG+FSL-1 to induce protection against an intranasal (i.n.) C. muridarum challenge, female mice were vaccinated intramuscularly (i.m.) or i.n. and i.m. simultaneously 4 weeks apart. Following vaccination with MOMP-tNLP+CpG+FSL-1, mice mounted significant humoral and cell-mediated immune responses. Following the i.n. challenge, mice vaccinated with MOMP-tNLP+CpG+FSL-1 i.n. + i.m. group were protected as determined by the percentage change in body weight and by the number of C. muridarum inclusion forming units (IFU) recovered from the lungs. To our knowledge, this is the first time a MOMP-based vaccine formulated in tNLP has been shown to protect against C. muridarum. MDPI 2021-07-07 /pmc/articles/PMC8310061/ /pubmed/34358171 http://dx.doi.org/10.3390/vaccines9070755 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tifrea, Delia F.
He, Wei
Pal, Sukumar
Evans, Angela C.
Gilmore, Sean F.
Fischer, Nicholas O.
Rasley, Amy
Coleman, Matthew A.
de la Maza, Luis M.
Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title_full Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title_fullStr Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title_full_unstemmed Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title_short Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles
title_sort induction of protection in mice against a chlamydia muridarum respiratory challenge by a vaccine formulated with the major outer membrane protein in nanolipoprotein particles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310061/
https://www.ncbi.nlm.nih.gov/pubmed/34358171
http://dx.doi.org/10.3390/vaccines9070755
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