Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi.

Frontiers in Immunology
Andrés Sánchez AlbertiEmilio L Malchiodi

Abstract

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.

References

Apr 8, 1998·The American Journal of Physiology·G F MitchellG Koren
Jun 12, 2003·Molecular and Biochemical Parasitology·Kara L Cummings, Rick L Tarleton
Jun 8, 2004·The Journal of Infectious Diseases·Marikena G RissoM Susana Leguizamon
Mar 8, 2008·Nature Reviews. Immunology·Robert A SederMario Roederer
Feb 20, 2010·PLoS Neglected Tropical Diseases·Paulo Marcos da Matta GuedesJoão S Silva
Apr 20, 2010·Lancet·Anis RassiJosé Antonio Marin-Neto
Jun 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoshiyuki MiyazakiHiroki Yoshida
Aug 27, 2010·The Journal of Parasitology·Christopher S EickhoffDaniel F Hoft
Mar 17, 2011·PLoS Neglected Tropical Diseases·Oscar FranzénBjörn Andersson
Dec 4, 2012·The Journal of Infectious Diseases·Luisa M D MagalhãesWalderez O Dutra
Nov 20, 2013·Journal of Pharmacology & Pharmacotherapeutics·Jaykaran Charan, N D Kantharia
Aug 28, 2014·The Journal of Infectious Diseases·Silvia I CazorlaEmilio L Malchiodi
Dec 17, 2014·Expert Review of Vaccines·Fernando J Sánchez-ValdézMiguel Ángel Basombrío
Apr 30, 2015·Seminars in Immunopathology·Rick L Tarleton
Feb 3, 2016·Trends in Immunology·Nathan D PennockRoss M Kedl
Feb 26, 2016·PLoS Neglected Tropical Diseases·Bernard PecoulPeter J Hotez
May 19, 2017·Nature Immunology·Marc Veldhoen
Mar 31, 2018·PLoS Neglected Tropical Diseases·Augusto E BivonaEmilio L Malchiodi
Apr 20, 2018·MMWR. Morbidity and Mortality Weekly Report·Sarah SchillieNoele Nelson
Oct 27, 2018·Frontiers in Immunology·Jimena Tosello BoariEva V Acosta Rodríguez
Dec 12, 2018·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Edmundo J N CamaraManoel Barral-Netto

❮ Previous
Next ❯

Citations

Feb 4, 2021·Tropical Medicine and Infectious Disease·Eric Dumonteil, Claudia Herrera

❮ Previous
Next ❯

Methods Mentioned

BETA
flow-cytometry
PCR
FACS
flow cytometry

Software Mentioned

QQPLOT
ImmunoSpot image analyzer
FlowJo
R
GraphPad Prism

Related Concepts