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Investigation

Pneumococcus

Research Lines

Content with Investigacion Inmunopatología del SIDA .

Research Lines:

1.    Molecular mechanisms associated to the protection of HIV-1 infection in limb-girdle muscular dystrophy dominant D2 (LGMDD2) patients.
2.    Generation of neutralizing antibodies for therapeutic use based on the broad-spectrum neutralizing response against founder viruses.
3.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age.
4.    Screening and characterization of new anti-latency drugs against HIV-1.
5.    Study of viral entry and HIV tropism in viruses of special epidemiological relevance in Spain. 
6.    Genetic mechanisms of protection and control of HIV-1 infection in populations with extreme phenotypes.

Clinical studies:

1.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine as a preventive vaccine in healthy uninfected adults. 
2.    ENE-COVID-Senior: Prospective observational study in a cohort of elderly nursing home residents to establish their immune status after receiving a complete vaccination regimen.

Implementation of new technologies:

1.    Identification of HIV-1 integration sites by deep sequencing.
2.    Single cell transcriptomics with simultaneous TCR/BCR sequencing.
3.    Epidemiological intelligence for prediction of SARS-CoV-2 variants likely to emerge in different vaccination settings.
 

Research projects

Content with Investigacion Inmunopatología del SIDA .

1.    Immune response to SARS-CoV-2 infection: effect in naïve vaccinees and seropositives against the most transmissible variants and relevance of host genetics.
Principal Investigator: Javier García Pérez. 
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 135.000 €
Duration: 2022-2025. 
Project Reference: PI21CIII/00025.
2.    Design and generation of viral stocks of new SARS-CoV-2 variants (omicron subvariants) and analysis of their susceptibility to antibodies neutralization.
Principal Investigator: Javier García Pérez.
Funding Agency: Hipra Scientific S.L.U.
Funding: 103.771 €
Duration: 2023-2025.
Project Reference: MVP 198/23.
3.    Characterization of a mutation in transportin 3 that protects against HIV infection: molecular mechanisms and discovery of new drugs.
Principal Investigator: José Alcamí y Javier García Pérez.
Funding Agency:     Proyectos de I+D+I, Generación de Conocimiento y Retos Investigación de la Agencia Estatal de Investigación.
Funding: 240.000 €
Duration: 2022-2026. 
Project Reference: PID2021-125978OB-C21 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE

4.    Generation of immunogens based on HIV-1 envelopes from acutely infected individuals with a broad neutralizing response against founder viruses.
Principal investigator: Nuria González Fernández.
Funding Agency: Acción Estratégica en Salud Intramural 2023 (ISCIII)
Funding: 82.000 €
Duration: 2024-2026. 
Project Reference: PI23CIII/00039.
5.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine. 
Principal Investigator: Josep Mallolas Masferrer.
Funding Agency: Proyectos de Investigación Clínica Independiente, Acción Estratégica en Salud 2021-2023 (ISCIII).
Funding: 173.200 €
Duration: 2024-2026. 
Project Reference: ICI23/00025.
6.    Service of immunological determinations of the ENE-COVID SENIOR II protocol.
Principal Investigator: Mayte Pérez Olmeda y Javier García Pérez. 
Funding Agency: Fundación para la investigación biomédica del Hospital Universitario La Paz
Funding: 185.037 €
Duration: 2024-2025. 
Project Reference: MOTR 219/24.
7.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age using single cell transcriptomics.
Principal Investigator: Javier García Pérez y Francisco Díez Fuertes.
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 152.000 €
Duration: 2025-2027. 
Project Reference: PI24CIII/00058
8. Evaluation of rimonabant and cannbinooid analogues in HIV infection and viral latency.
Principal Investigator: Luis Miguel Bedoya del Olmo. 
Funding Agency: Universidad Complutense de Madrid
Funding: 12.000 €
Duration: 2024-2025. 
Project Reference: PR12/24-31553.
9. Discovery of new inhibitors of HIV-1 RNA biogenesis based on blocking the ribonucleoprotein RRE-Rev.
Principal Investigator: José Gallego Sala. Associate Researcher: Luis Miguel Bedoya del Olmo
Funding Agency: Department of Innovation, Universities, Science and Digital Society. Generalitat Valenciana.
Funding: 543,683.84 €
Duration: 2025-2027. 
Project Reference: PROMETEO/2021/036.

Publications

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Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter.

9. Muñoz-Sanz A, Rodríguez Vidigal FF, Vera-Tome A, Jimenez MS. Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter. Enfer Infecc Microbiol Clin. 2013; 31:59-6

PUBMED DOI

Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.

2. Gil H, Fernández-García A*, Mosquera MM, Hübschen JM, Castellanos AM, de Ory F, Masa-Calles J, Echevarría JE.Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain. PLoS One. 2018 Jul. 16;13(7):e0199975. * Corresponding author.

PUBMED DOI

Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus

3. Banyard AC, Selden D, Wu G; Thorne L, Jennings D, Marston D, Finke S, Freuling CM, Mueller T, Echevarria JE, Fooks AR. Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus. Journal of General Virology, 2018. 99(12):1590-1599

PUBMED DOI

Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population

6. López-Perea N, Masa-Callesa J, Torres de Miera MV, Fernández-García A, Echevarría JE, de Ory F, Martínez de Aragón MV. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine, 2017, 35(34): 4339-4345.

PUBMED DOI

Genetic characterization of rubella virus strains detected in Spain, 1998-2014.

8. Martínez-Torres AO, Mosquera MM, De Ory F, González-Praetorius A, Echevarría JE. Genetic characterization of rubella virus strains detected in Spain, 1998-2014. PLoS ONE. 2016. 11(9):e0162403.

PUBMED DOI

Novel Lyssavirus in bat, Spain

9. Aréchiga-Ceballos N, Vázquez-Morón S, Berciano JM, Nicolás O, Aznar- López C, Juste J, Rodríguez-Nevado C, Aguilar-Setién A, Echevarría JE. Novel Lyssavirus in bat, Spain. Emerging infectious Diseases. 2013.19(5): 793-795.

PUBMED DOI

The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years

2. Trento A, Rodriguez-Fernandez R, Gonzalez-Sanchez MI, Gonzalez-Martinez F, Mas V, Vazquez M, et al. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years. Front Microbiol. 2017;8:2301.

PUBMED DOI

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

3. Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun. 2017;8:14158.

PUBMED DOI

Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors

6. Gilman MS, Castellanos CA, Chen M, Ngwuta JO, Goodwin E, Moin SM, et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol. 2016;1(6).

PUBMED DOI

Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.

8. Gilman MS, Moin SM, Mas V, Chen M, Patel NK, Kramer K, et al. Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog. 2015;11(7):e1005035.

PUBMED DOI

Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.

 9. Palomo C, Mas V, Vazquez M, Cano O, Luque D, Terron MC, et al. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology. 2014;460-461:119-27.

PUBMED DOI

Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus

Jiménez-Zaragoza M., Yubero M.L., Martín-Forero E., Castón J.R., Reguera D., Luque D.*, de Pablo P.J., Rodríguez J.M. 2018. Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus. eLife 7: e37295. *Corresponding author.

PUBMED DOI

Capsid structure of dsRNA fungal viruses.

Luque D., Mata C.P., Suzuki N., Ghabrial S.A., Castón J.R. 2018. Capsid structure of dsRNA fungal viruses. Viruses 10(9):481

PUBMED DOI

Structural insights into Rotavirus entry

Rodríguez J.M., Luque D.* 2019. Structural insights into Rotavirus entry. Advances in Experimental Medicine and Biology. 1215:45-68. *Corresponding author.

PUBMED DOI

Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses

Mata C.P., Luque D., Gómez-Blanco J., Rodríguez J.M., González J.M., Suzuki N., Ghabrial S.A., Carrascosa J.L., Trus B.L., Castón J.R. 2017. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 13(12):e1006755.

PUBMED DOI

Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes

Sarker S., C. Terrón M., Khandokar Y., Aragão D., Hardy J.M., Radjainia M., Jiménez-Zaragoza M., de Pablo P.J., Coulibaly F., Luque D., Raidal D.R., Forwood J.K. 2016. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nat. Commun. 7:13014. IF: 12.124; D1.

PUBMED DOI

Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1

Luque D., Mata C.P., González-Camacho F., González J.M., Gómez-Blanco J., Alfonso C., Rivas G., Havens W.M., Kanematsu S., Suzuki N., Ghabrial S.A., Trus B.L., Castón J.R. 2016. Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1. J Virol. 90(24):11220-11230. IF: 4.666, Q1.

PUBMED DOI

Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage

Luque D., de la Escosura A., Snijder J., Brasch M., Burnley R.J, Koay M.S.T., Carrascosa J.L., Wuite G.J.L., Roos W.H., Heck A.J.R., J.J.L.M Cornelissen, Torres T., Castón J.R. 2014. Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage. Chem. Sci.,5, 575-581. IF: 9.211, D1.

DOI

Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.

Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1

PUBMED DOI

New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage

Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.

PUBMED DOI

Content with Investigacion Inmunopatología del SIDA .

List of staff

Additional Information

The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen. 

Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria. 

Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.

The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen. 

Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria. 

Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.

Content with Investigacion Inmunopatología del SIDA .