Análisis de anticuerpos monoclonales contra la región MPER de la proteína de envuelta del VIH-1. Aplicación del diseño de inmunógenos


Neutralizing antibodies isolated from HIV infected individuals protect from HIV infection in different animal models. However, such antibodies are not elicited by current vaccine candidates. The membrane proximal external region (MPER) of the gp41 subunit of HIV envelope glycoprotein is a potential target to generate neutralizing antibodies, although its hydrophobicity and membrane proximity may impose some limitations. Our previous work has identified a gp41 derived miniprotein useful to identify anti MPER humoral responses in HIV infected individuals and able to generate strong humoral responses in murine models, specially when administered in proteoliposomal formulations.

Despite these promising data, our results demonstrate that both infected individuals and inmunized animals show heterogeneous neutralizing and nonneutralizing responses against the MPER. Therefore, in this project we plan to learn from this data to further develop our immunogens according to the following objectives:

    1-To define structural determinants associated with neutralizing and nonneutralizing antibody activity.

    2-To define the role of proteoliposomal lipids in protein structure and the development of immune responses.

    3-To integrate these data on a new improved immunogen design. 

Methodology involves epitope mapping, monoclonal antibody isolation and mutagenesis, molecular modeling and murine models of immunization.

Date: 01/01/2015

Duration: : 2015-2017

Financing entity: Fondo de Investigación Sanitaria, Spanish Ministry of Health

Research Supervisor(s): Julià Blanco

IrsiCaixa linked groups: Cell Virology and Immunology