Identification of human antibody molecules that neutralize viral infections
Identification of human antibody molecules that neutralize viral infections
Adaptive immunity against viral infections is mediated by humoral and cellular immune responses. The efficacy of the humoral response depends on the production of antibodies (Ab) that prevent virus entry into host cells and infection. Ab mainly target extracellular viruses and they inhibit initial infection and cell-to-cell transfer. Among the Ab generated during the course of an infection or after vaccination, a subset is highly protective and successfully neutralize the infection. Potent neutralizing Ab (nAb) bind to proteins exposed on viral particles. In enveloped viruses, the spike proteins are the main targets of nAb; they usually recognize invariant protein regions, some used in virus binding to cell surface molecules and cell entry. Vaccinations can easily generate potent nAb against viruses with low mutation rate and variability, for example measles virus (MV). In contrast, viruses that evolve quickly such as human immunodeficiency virus (HIV), with constant changes in their envelope proteins, are difficult to neutralize and vaccination does not provide long time protection.
Ab are well-established therapeutics and presently an exciting area for collaborative research and development in industry and academia. Most therapeutic Ab are used in the treatment of cancer (51%) and autoimmune diseases (38%) and still few for infectious diseases (2.4%). This is a small number of therapeutic Ab, but they are expected to account for half of the top selling drugs in 2014. Thus, this is a fast growing sector of the pharmaceutical market. The development of Ab-related biotechnologies and the design of therapeutic Ab will have a relevant social impact in the coming years. Recent reports on the therapeutic use of Ab for the treatment of HIV showed these molecules can be effective for the treatment of complex viral infections.
The aim of the TFM project is the identification of Ebola or Measles virus-neutralizing human Ab using phage display technologies. Measles is responsible of recurrent outbreaks in populated areas of Western countries, spreading through the infection of unvaccinated newborns and adults. Ebola virus is highly pathogenic and generated the serious 2014-2016 epidemy in Africa that spread to Spain, UK and USA. Development of new therepeutic Ab preventing Ebola or Measles virus infections is thus an important research challenge for Health improvement.