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A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite

The design of efficient vaccines for long-term protective immunity against pathogens represents an objective of utmost public health priority. In general, live attenuated vaccines are considered to be more effective than inactivated pathogens, yet potentially more reactogenic. Accordingly, inactivat...

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Autores principales: Rotem, Shahar, Bar-Haim, Erez, Elia, Uri, Cohen, Hila, Lazar, Shirley, Cohen, Ofer, Chitlaru, Theodor, Gal, Yoav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607248/
https://www.ncbi.nlm.nih.gov/pubmed/36298458
http://dx.doi.org/10.3390/vaccines10101593
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author Rotem, Shahar
Bar-Haim, Erez
Elia, Uri
Cohen, Hila
Lazar, Shirley
Cohen, Ofer
Chitlaru, Theodor
Gal, Yoav
author_facet Rotem, Shahar
Bar-Haim, Erez
Elia, Uri
Cohen, Hila
Lazar, Shirley
Cohen, Ofer
Chitlaru, Theodor
Gal, Yoav
author_sort Rotem, Shahar
collection PubMed
description The design of efficient vaccines for long-term protective immunity against pathogens represents an objective of utmost public health priority. In general, live attenuated vaccines are considered to be more effective than inactivated pathogens, yet potentially more reactogenic. Accordingly, inactivation protocols which do not compromise the pathogen’s ability to elicit protective immunity are highly beneficial. One of the sentinel mechanisms of the host innate immune system relies on the production of reactive nitrogen intermediates (RNI), which efficiently inactivate pathogens. Peroxynitrite (PN) is a prevalent RNI, assembled spontaneously upon the interaction of nitric oxide (NO) with superoxide. PN exerts its bactericidal effect by via the efficient oxidation of a broad range of biological molecules. Furthermore, the interaction of PN with proteins results in structural/chemical modifications, such as the oxidation of tryptophan, tyrosine, and cysteine residues, as well as the formation of carbonyl, dityrosine, and nitrotyrosine (NT). In addition to their role in innate immunity, these PN-mediated modifications of pathogen components may also augment the antigenicity of pathogen peptides and proteins, hence contributing to specific humoral responses. In the study reported here, a novel approach for vaccine development, consisting of pathogen inactivation by PN, combined with increased immunity of NT-containing peptides, is implemented as a proof-of-concept for vaccination against the intracellular pathogen Francisella tularensis (F. tularensis). In vivo experiments in a murine model of tularemia confirm that PN-inactivated F. tularensis formulations may rapidly stimulate innate and adaptive immune cells, conferring efficient protection against a lethal challenge, superior to that elicited by bacteria inactivated by the widely used formalin treatment.
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spelling pubmed-96072482022-10-28 A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite Rotem, Shahar Bar-Haim, Erez Elia, Uri Cohen, Hila Lazar, Shirley Cohen, Ofer Chitlaru, Theodor Gal, Yoav Vaccines (Basel) Article The design of efficient vaccines for long-term protective immunity against pathogens represents an objective of utmost public health priority. In general, live attenuated vaccines are considered to be more effective than inactivated pathogens, yet potentially more reactogenic. Accordingly, inactivation protocols which do not compromise the pathogen’s ability to elicit protective immunity are highly beneficial. One of the sentinel mechanisms of the host innate immune system relies on the production of reactive nitrogen intermediates (RNI), which efficiently inactivate pathogens. Peroxynitrite (PN) is a prevalent RNI, assembled spontaneously upon the interaction of nitric oxide (NO) with superoxide. PN exerts its bactericidal effect by via the efficient oxidation of a broad range of biological molecules. Furthermore, the interaction of PN with proteins results in structural/chemical modifications, such as the oxidation of tryptophan, tyrosine, and cysteine residues, as well as the formation of carbonyl, dityrosine, and nitrotyrosine (NT). In addition to their role in innate immunity, these PN-mediated modifications of pathogen components may also augment the antigenicity of pathogen peptides and proteins, hence contributing to specific humoral responses. In the study reported here, a novel approach for vaccine development, consisting of pathogen inactivation by PN, combined with increased immunity of NT-containing peptides, is implemented as a proof-of-concept for vaccination against the intracellular pathogen Francisella tularensis (F. tularensis). In vivo experiments in a murine model of tularemia confirm that PN-inactivated F. tularensis formulations may rapidly stimulate innate and adaptive immune cells, conferring efficient protection against a lethal challenge, superior to that elicited by bacteria inactivated by the widely used formalin treatment. MDPI 2022-09-22 /pmc/articles/PMC9607248/ /pubmed/36298458 http://dx.doi.org/10.3390/vaccines10101593 Text en © 2022 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
Rotem, Shahar
Bar-Haim, Erez
Elia, Uri
Cohen, Hila
Lazar, Shirley
Cohen, Ofer
Chitlaru, Theodor
Gal, Yoav
A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title_full A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title_fullStr A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title_full_unstemmed A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title_short A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite
title_sort novel approach to vaccine development: concomitant pathogen inactivation and host immune stimulation by peroxynitrite
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607248/
https://www.ncbi.nlm.nih.gov/pubmed/36298458
http://dx.doi.org/10.3390/vaccines10101593
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