Gut microbiome and clinical and lifestyle host factors associated with recurrent positive RT-PCR for SARS-CoV-2 DOI Creative Commons

Cristina Jiménez-Arroyo,

Natalia Molinero, Carlos Sabater

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 18, 2024

Background SARS-CoV-2 and COVID-19 are still active in the population. Some patients remained PCR-positive for more than 4 weeks, called “persistently PCR-positive”. Recent evidence suggests a link between gut microbiota susceptibility to COVID-19, although no studies have explored persistent PCR conditions. We aimed evaluate relationship positive RT-PCR, microbiome, individual host determinants. Methods A shotgun metagenomic analysis was conducted on fecal samples from 28 individuals affected by COVID-19. Patients were divided into two groups: those who had cleared virus within 30 days (designated as control group) (n = 15), beyond (called PCR+ 13). also investigated correlation prolonged viral clearance several additional factors, including clinical parameters, immune responses, microbial metabolites, dietary habits. Results The composition functionality of microbiome varied based duration positivity determined PCR. Compared group, group exhibited elevated pathogen levels augmented diversity functional gene families (p-value < 0.05). multi-omics integrating metagenomics, metadata revealed specific contribution certain blood markers this basophils, IgM, IgG (both general SARS-CoV-2), liver damage. Unhealthy diet identified significant factor influencing positivity. Conclusions These findings indicate that may play role delayed RT-PCR results. Our study contributes understanding factors mediators linking disease outcomes. Further large-scale must confirm these data; however, they suggest relevance monitoring changes early post-viral years providing healthcare support.

Language: Английский

Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates DOI Creative Commons
Ekaterina Stepanova,

Irina Isakova-Sivak,

Victoria Matyushenko

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1099 - 1099

Published: Sept. 26, 2024

Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted attenuated influenza (LAIV) H3N2 subtype, which expressed immunogenic T-cell epitopes. A cassette encoding fragments S N proteins was inserted into NA gene using P2A autocleavage site. In this study, we present results preclinical evaluation in non-human primate model.

Language: Английский

Citations

2
Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium DOI Creative Commons
Laura Marcos-Villar, Beatriz Perdiguero, María López‐Bravo

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity emergence resistant variants underscore need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing trimeric form receptor binding domain (RBD) spike (S) protein compared to homologous MVA/MVA regimen. In C57BL/6 mice, RBD was delivered during priming via an vector encapsulated nanoemulsions (NE) or lipid nanoparticles (LNP), followed by booster with replication-deficient MVA-based recombinant (MVA-RBD). mRNA/MVA elicited strong anti-RBD neutralizing antibodies (BAbs NAbs) against both ancestral strain different concern (VoCs). Additionally, this protocol induced robust polyfunctional RBD-specific CD4 CD8 T cell responses, particularly animals primed mLNP-RBD. K18-hACE2 transgenic LNP-RBD/MVA combination provided complete protection from mortality following live challenge partial observed mNE-RBD/MVA regimens. Although only protects half animals, it able induce Fc-mediated effector functions besides NAbs. Moreover, viral replication load respiratory tract were markedly reduced decreased pro-inflammatory cytokine levels observed. These results support efficacy vaccine combinations over regimen, using alternative nanocarriers that circumvent intellectual property restrictions formulations.

Language: Английский

Citations

1
Rendezvous with Vaccinia Virus in the Post-smallpox Era: R&D Advances DOI Creative Commons
Yuxiang Wang

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1742 - 1742

Published: Aug. 15, 2023

Smallpox was eradicated in less than 200 years after Edward Jenner’s practice of cowpox variolation 1796. The forty-three us living free smallpox, beginning 1979, never truly separated from poxviruses. recent outbreak monkeypox May 2022 might well warn the necessity keeping up both scientific research and public awareness One them particular, vaccinia virus (VACV), has been extensively studied as a vector given its broad host range, extraordinary thermal stability, exceptional immunogenicity. Unceasing fundamental biological on VACV provides with better understanding genetic elements, involvement cellular signaling pathways, modulation immune responses. This enables rational design safer more efficacious next-generation vectors. To address new technological advancement within past decade research, this review covers studies viral immunomodulatory genes, modifications commonly used vectors, novel mechanisms for rapid generation purification recombinant virus, several other innovative approaches to studying biology.

Language: Английский

Citations

2
B and T Cell Bi-Cistronic Multiepitopic Vaccine Induces Broad Immunogenicity and Provides Protection Against SARS-CoV-2 DOI Creative Commons
Beatriz Perdiguero, Enrique Álvarez, Laura Marcos-Villar

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(11), P. 1213 - 1213

Published: Oct. 25, 2024

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for vaccines targeting both neutralizing antibodies (NAbs) and long-lasting cross-reactive T cells covering multiple viral proteins to provide broad durable protection against emerging variants. Methods: To address this, here we developed two vaccine candidates, namely (i) DNA-CoV2-TMEP, expressing multiepitopic CoV2-TMEP protein containing immunodominant conserved cell regions from SARS-CoV-2 structural proteins, (ii) MVA-CoV2-B2AT, encoding a bi-cistronic construct that combines B overlapping proteins. Results: Both candidates were assessed in vitro vivo demonstrating their ability induce robust immune responses. In C57BL/6 mice, DNA-CoV2-TMEP enhanced recruitment of innate stimulated SARS-CoV-2-specific polyfunctional MVA-CoV2-B2AT elicited NAbs various variants concern (VoCs) reduced replication yields Beta variant susceptible K18-hACE2 mice. combination with mutated ISG15 form as an adjuvant further increased magnitude, breadth profile response. Conclusion: These findings underscore potential these when expressed DNA or MVA vectors its variants, supporting development next-generation vaccines.

Language: Английский

Citations

0
Gut microbiome and clinical and lifestyle host factors associated with recurrent positive RT-PCR for SARS-CoV-2 DOI Creative Commons

Cristina Jiménez-Arroyo,

Natalia Molinero, Carlos Sabater

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 18, 2024

Background SARS-CoV-2 and COVID-19 are still active in the population. Some patients remained PCR-positive for more than 4 weeks, called “persistently PCR-positive”. Recent evidence suggests a link between gut microbiota susceptibility to COVID-19, although no studies have explored persistent PCR conditions. We aimed evaluate relationship positive RT-PCR, microbiome, individual host determinants. Methods A shotgun metagenomic analysis was conducted on fecal samples from 28 individuals affected by COVID-19. Patients were divided into two groups: those who had cleared virus within 30 days (designated as control group) (n = 15), beyond (called PCR+ 13). also investigated correlation prolonged viral clearance several additional factors, including clinical parameters, immune responses, microbial metabolites, dietary habits. Results The composition functionality of microbiome varied based duration positivity determined PCR. Compared group, group exhibited elevated pathogen levels augmented diversity functional gene families (p-value < 0.05). multi-omics integrating metagenomics, metadata revealed specific contribution certain blood markers this basophils, IgM, IgG (both general SARS-CoV-2), liver damage. Unhealthy diet identified significant factor influencing positivity. Conclusions These findings indicate that may play role delayed RT-PCR results. Our study contributes understanding factors mediators linking disease outcomes. Further large-scale must confirm these data; however, they suggest relevance monitoring changes early post-viral years providing healthcare support.

Language: Английский

Citations

0