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Article ; Online: Editorial: The regulatory immune system as a target to improve adjuvants and novel vaccines.

Jiménez-Cortegana, Carlos / Poveda, Cristina / Cabrera, Gabriel

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1223689

MeSH term(s)	Vaccines ; Immune System ; Adjuvants, Immunologic/pharmacology
Chemical Substances	Vaccines ; Adjuvants, Immunologic
Language	English
Publishing date	2023-06-05
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1223689
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Article ; Online: Mining the Metabolome for New and Innovative Chagas Disease Treatments.

Poveda, Cristina / Bottazzi, Maria Elena / Jones, Kathryn M

Trends in pharmacological sciences

2020 Volume 42, Issue 1, Page(s) 1–3

Abstract: Identifying novel therapeutic targets for Chagas disease is a scientific priority. Recently, Hossain et al. used an innovative metabolomic approach to define disease tolerance mechanisms and identify therapeutic targets for Chagas disease. This is the ... ...

Abstract	Identifying novel therapeutic targets for Chagas disease is a scientific priority. Recently, Hossain et al. used an innovative metabolomic approach to define disease tolerance mechanisms and identify therapeutic targets for Chagas disease. This is the first study translating metabolomic data to develop novel treatments for Chagas disease.
MeSH term(s)	Animals ; Chagas Disease/drug therapy ; Humans ; Metabolome ; Microbiota ; Parasites ; Tropism ; Trypanosoma cruzi
Language	English
Publishing date	2020-11-25
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2020.11.007
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Article ; Online: Preclinical advances and the immunophysiology of a new therapeutic Chagas disease vaccine.

Jones, Kathryn M / Poveda, Cristina / Versteeg, Leroy / Bottazzi, Maria Elena / Hotez, Peter J

Expert review of vaccines

2022 Volume 21, Issue 9, Page(s) 1185–1203

Abstract: Introduction: Chronic infection with the protozoal parasite : Areas covered: We report on our current understanding of the underlying immunologic and physiologic mechanisms that lead to CCC, including parasite immune escape mechanisms that allow ... ...

Abstract	Introduction: Chronic infection with the protozoal parasite Areas covered: We report on our current understanding of the underlying immunologic and physiologic mechanisms that lead to CCC, including parasite immune escape mechanisms that allow persistence and the subsequent inflammatory and fibrotic processes that lead to clinical disease. We report on vaccine design and the observed immunotherapeutic effects including induction of a balanced T Expert opinion: Our vaccine-linked chemotherapeutic approach is a multimodal treatment strategy, addressing both the parasite persistence and the underlying deleterious host inflammatory and fibrotic responses that lead to cardiac dysfunction. In targeting treatment towards patients with chronic indeterminate or early determinate Chagas disease, this vaccine-linked chemotherapeutic approach will be highly economical and will reduce the global disease burden and deaths due to CCC.
MeSH term(s)	Chagas Disease/prevention & control ; Humans ; Trypanosoma cruzi ; Vaccines
Chemical Substances	Vaccines
Language	English
Publishing date	2022-07-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2022.2093721
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Article: The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic

Nguyen, Duc Minh / Poveda, Cristina / Pollet, Jeroen / Gusovsky, Fabian / Bottazzi, Maria Elena / Hotez, Peter J / Jones, Kathryn M

bioRxiv : the preprint server for biology

2023

Abstract: Background: Chagas disease, chronic infection with : Methodology: Female BALB/c mice were infected with a bioluminescent : Results: Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular ... ...

Abstract	Background: Chagas disease, chronic infection with Methodology: Female BALB/c mice were infected with a bioluminescent Results: Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. Conclusions: These data confirm toxicity associated with curative doses of BNZ and suggest that the dose sparing low BNZ plus vaccine treatment better preserves liver health.
Language	English
Publishing date	2023-07-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.11.548497
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Article ; Online: The impact of vaccine-linked chemotherapy on liver health in a mouse model of chronic Trypanosoma cruzi infection.

Nguyen, Duc Minh / Poveda, Cristina / Pollet, Jeroen / Gusovsky, Fabian / Bottazzi, Maria Elena / Hotez, Peter J / Jones, Kathryn Marie

PLoS neglected tropical diseases

2023 Volume 17, Issue 11, Page(s) e0011519

Abstract: Background: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug ... ...

Abstract	Background: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. Methodology: Female BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25μg Tc24-C4 protein/ 5μg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum. Results: Curative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact. Conclusions: These data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not reduce parasite burdens, it better preserves liver health.
MeSH term(s)	Female ; Animals ; Mice ; Hepatomegaly/drug therapy ; Persistent Infection ; PPAR alpha/pharmacology ; PPAR alpha/therapeutic use ; Chagas Disease/drug therapy ; Chagas Disease/prevention & control ; Chagas Disease/parasitology ; Trypanosoma cruzi ; Vaccines ; Nitroimidazoles ; Trypanocidal Agents/pharmacology
Chemical Substances	PPAR alpha ; Vaccines ; Nitroimidazoles ; Trypanocidal Agents
Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0011519
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Article ; Online: The zebrafish as a potential model for vaccine and adjuvant development.

Hotez, Peter J / Bottazzi, Maria Elena / Islam, Nelufa Yesmin / Lee, Jungsoon / Pollet, Jeroen / Poveda, Cristina / Strych, Ulrich / Thimmiraju, Syamala Rani / Uzcategui Araujo, Nestor / Versteeg, Leroy / Gorelick, Daniel

Expert review of vaccines

2024

Abstract: Introduction: Zebrafishesrepresent a proven model for human diseases and systems biology, exhibitingphysiological and genetic similarities and having innate and adaptive immunesystems. However, they are underexplored for human vaccinology, ... ...

Abstract	Introduction: Zebrafishesrepresent a proven model for human diseases and systems biology, exhibitingphysiological and genetic similarities and having innate and adaptive immunesystems. However, they are underexplored for human vaccinology, vaccinedevelopment, and testing. Here we summarize gaps and challenges. Areas covered: Zebrafish models have fourpotential applications: 1) Vaccine safety: The pastsuccesses in using zebrafishes to test xenobiotics could extend to vaccine andadjuvant formulations for general safety or target organs due to the zebrafish embryos'optical transparency. 2) Innate immunity: The zebrafish offers refined ways toexamine vaccine effects through signaling via Toll-like or NOD-like receptors inzebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunologicalreagents for challenge studies. 4) Systems vaccinology: Due to the availabilityof a well-referenced zebrafish genome, transcriptome, proteome, and epigenome,this model offers potential here. Expert opinion: It remains unproven whether zebrafishes can beemployed for testing and developing human vaccines. We are still at thehypothesis-generating stage, although it is possible to begin outliningexperiments for this purpose. Throughtransgenic manipulation, zebrafish models could offer new paths for shapinganimal models and systems vaccinology.
Language	English
Publishing date	2024-04-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2024.2345685
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Article: Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens.

Poveda, Cristina / Biter, Amadeo B / Bottazzi, Maria Elena / Strych, Ulrich

Vaccines

2019 Volume 7, Issue 4

Abstract: The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to ... ...

Abstract	The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to traditional vaccine development platforms, and thus there is less clarity regarding the criteria needed to ensure regulatory compliance and acceptance. Generally, to identify the ideal product characteristics, a series of assays needs to be developed, qualified and ultimately validated to determine the integrity, purity, stability, and reproducibility of a vaccine target. Here, using the available literature, we provide a summary of the array of biophysical and biochemical assays currently used in the field to characterize mRNA vaccine antigen candidates. Moreover, we review various in vitro functional cell-based assays that have been employed to facilitate the early assessment of the biological activity of these molecules, including the predictive immune response triggered in the host cell. Messenger RNA vaccines can be produced rapidly and at large scale, and thus will particularly benefit from well-defined and well-characterized assays ultimately to be used for in-process, release and stability-indications, which will allow equally rapid screening of immunogenicity, efficacy, and safety without the need to conduct often lengthy and costly in vivo experiments.
Language	English
Publishing date	2019-09-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines7040131
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Article ; Online: Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease.

Mancino, Chiara / Pollet, Jeroen / Zinger, Assaf / Jones, Kathryn M / Villar, Maria José / Leao, Ana Carolina / Adhikari, Rakesh / Versteeg, Leroy / Tyagi Kundu, Rakhi / Strych, Ulrich / Giordano, Federica / Hotez, Peter J / Bottazzi, Maria Elena / Taraballi, Francesca / Poveda, Cristina

ACS applied materials & interfaces

2024 Volume 16, Issue 13, Page(s) 15832–15846

Abstract: Chagas disease (CD) (American trypanosomiasis caused ... ...

Abstract	Chagas disease (CD) (American trypanosomiasis caused by
MeSH term(s)	Mice ; Animals ; RNA ; Tissue Distribution ; Protozoan Vaccines ; Chagas Disease/prevention & control ; Antigens, Protozoan/genetics ; RNA, Messenger ; Technology
Chemical Substances	RNA (63231-63-0) ; Protozoan Vaccines ; Antigens, Protozoan ; RNA, Messenger
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c18830
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Article ; Online: Microbiome Alterations Driven by

Castañeda, Sergio / Muñoz, Marina / Hotez, Peter J / Bottazzi, Maria Elena / Paniz-Mondolfi, Alberto E / Jones, Kathryn M / Mejia, Rojelio / Poveda, Cristina / Ramírez, Juan David

Microbiology spectrum

2023 Volume 11, Issue 3, Page(s) e0019923

Abstract: Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host- ... ...

Abstract	Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal tissues, including changes in anti-inflammatory (interleukin-4 [IL-4] and IL-10) and proinflammatory (gamma interferon, tumor necrosis factor alpha, and IL-6) cytokines. Bacterial species such as Bacteroides thetaiotaomicron, Faecalibaculum rodentium, and Lactobacillus johnsonii showed a decrease in relative abundance, while Akkermansia muciniphila and Staphylococcus xylosus increased. Likewise, as infection progressed, there was a decrease in gene abundances related to metabolic processes such as lipid synthesis (including short-chain fatty acids) and amino acid synthesis (including branched-chain amino acids). High-quality metagenomic assembled genomes of L. johnsonii and A. muciniphila among other species were reconstructed, confirming, functional changes associated with metabolic pathways that are directly affected by the loss of abundance of specific bacterial taxa.
MeSH term(s)	Mice ; Animals ; Disease Models, Animal ; Mice, Inbred C57BL ; Chagas Disease/parasitology ; Trypanosoma cruzi ; Microbiota
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.00199-23
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Article ; Online: Immunomodulatory proteins from hookworms reduce cardiac inflammation and modulate regulatory responses in a mouse model of chronic

Jones, Kathryn M / Zhan, Bin / Ernste, Keenan J / Villar, Maria Jose / Bisht, Nalini / Nguyen, Duc / Chang, Li-Yen / Poveda, Cristina / Robinson, Gonteria J / Trivedi, Akshar J / Hofferek, Colby J / Decker, William K / Konduri, Vanaja

Frontiers in parasitology

2023 Volume 2

Abstract: Introduction: Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4 + Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 ... ...

Abstract	Introduction: Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4 + Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Methods: Female BALB/c mice infected with bioluminescent Results: Treatment with both AIP-1 and AIP-2 proteins significantly reduced cardiac cellular infiltration, and reduced cardiac levels of IFNγ, IL-6 and IL-2. AIP-2 treatment reduced cardiac expression of COX-2. Further, while incubation with AIP-1 and AIP-2 proteins did not induce a significant upregulation of an immunoregulatory phenotype in dendritic cells (DC), there was a modest upregulation of CD11c +CD11b+MHCII+SIRPα+ expression, suggesting a regulatory phenotype. Discussion: All
Language	English
Publishing date	2023-10-12
Publishing country	Switzerland
Document type	Journal Article
ISSN	2813-2424
ISSN (online)	2813-2424
DOI	10.3389/fpara.2023.1244604
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