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Article

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

Department of Molecular Genetics and Biochemistry, Israel Institute of Biological Research, Ness Ziona 74100, Israel
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Safder Ganaie
Vaccines 2022, 10(10), 1593; https://doi.org/10.3390/vaccines10101593 (registering DOI)
Received: 9 August 2022 / Revised: 7 September 2022 / Accepted: 19 September 2022 / Published: 22 September 2022
(This article belongs to the Special Issue Vaccine-Induced Reprogramming of Innate Immune Response)
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. View Full-Text
Keywords: reactive oxygen species; immunity; antigenicity reactive oxygen species; immunity; antigenicity
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MDPI and ACS Style

Rotem, S.; Bar-Haim, E.; Elia, U.; Cohen, H.; Lazar, S.; Cohen, O.; Chitlaru, T.; Gal, Y. A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite. Vaccines 2022, 10, 1593. https://doi.org/10.3390/vaccines10101593

AMA Style

Rotem S, Bar-Haim E, Elia U, Cohen H, Lazar S, Cohen O, Chitlaru T, Gal Y. A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite. Vaccines. 2022; 10(10):1593. https://doi.org/10.3390/vaccines10101593

Chicago/Turabian Style

Rotem, Shahar, Erez Bar-Haim, Uri Elia, Hila Cohen, Shirley Lazar, Ofer Cohen, Theodor Chitlaru, and Yoav Gal. 2022. "A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite" Vaccines 10, no. 10: 1593. https://doi.org/10.3390/vaccines10101593

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