Publications by authors named "B Perdiguero"

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 and durable protection against emerging variants.

Methods: To address this, here we developed two vaccine candidates, namely (i) DNA-CoV2-TMEP, expressing the multiepitopic CoV2-TMEP protein containing immunodominant and conserved T cell regions from SARS-CoV-2 structural proteins, and (ii) MVA-CoV2-B2AT, encoding a bi-cistronic multiepitopic construct that combines conserved B and T cell overlapping regions from SARS-CoV-2 structural proteins.

Results: Both candidates were assessed in vitro and in vivo demonstrating their ability to induce robust immune responses.

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Article Synopsis
  • Current SARS-CoV-2 mRNA vaccines are effective, but there's a need for new strategies due to waning immunity and variant emergence, prompting this study on a heterologous mRNA/MVA vaccination approach.
  • The research demonstrates that a combination of a trimeric receptor binding domain (RBD) delivered via mRNA and a modified vaccinia virus (MVA) boost creates strong immune responses, including effective antibodies and T cell activity against various SARS-CoV-2 strains.
  • The heterologous regimen provided complete protection in specific mouse models after exposure to the virus, outperforming traditional methods and suggesting that alternative nanocarrier technologies could enhance vaccine effectiveness while avoiding patent issues.
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  • - Vaccines using mRNA technology, particularly lipid nanoparticles (LNP), are key in combating SARS-CoV-2 and have applications for other diseases too.
  • - The study tested various lipid and polymer-based nanoparticles for delivering mRNA that encodes a part of the spike protein from SARS-CoV-2, assessing their toxicity and effectiveness in animal models.
  • - Results showed that modified lipid nanoparticles (mLNP) and traditional LNP-1 were highly effective in producing antibodies and protecting mice from COVID-19, suggesting alternative carriers can enhance mRNA vaccine performance.
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The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays a crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; and (iii) exerting extracellular cytokine activity. These various roles highlight its versatility in influencing numerous cellular pathways, encompassing DNA damage response, autophagy, antiviral response, and cancer-related processes, among others.

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