Human Monoclonal Antibodies Anti-Tetanus Toxoid

• Grant number: 11/22334-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2012
• End date: May 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ana Maria Moro
• Grantee: Eduardo Aliprandini
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Antibodies, mainly monoclonal, represent important tools for therapy and diagnosis, due to their high specificity towards the antigen. The studies with monoclonal antibodies started in the 70's when the hybridoma technology was devised. It meant, in subsequent years, a leap in understanding, monitoring and treating of many infections and pathologies. Notwithstanding, in several cases, only polyclonal antibodies obtained by the immunization of animals are available, as it is the case for clinical handling of infections by tetanus, diphtheria, rabies, botulism. Although their efficiency, confirmed by their utilization for longer than a century, polyclonal antibodies are of animal origin, consisting of heterologous proteins which can elicit immunogenicity, decreasing the efficacy and impairing possible future treatments. The focus of this project is tetanus toxoid. Tetanus is a neurological disease caused by the toxin produced by Clostridium tetani. Available treatments for tetanus infection, besides the vaccination, are those provided by hyperimmune sera produced in horses. In this project we aim to use an innovative methodology developed in Prof. Michel Nussenzweig's laboratory at the Rockfeller University for the generation of human monoclonal antibodies. The methodology makes use of identifying and selecting human B lymphocytes isolated from individuals who were vaccinated with anti-tetanus vaccine. The genes sequences of the selected B cells repertoire will be amplified and cloned in a vector suitable for expression in HEK cells. The produced variants will be purified and characterized by affinity, specificity, cross-reactions and neutralization ability. Besides the obtainment of human monoclonal antibodies against tetanus, the development of the methodology could be useful for the generation of human antibodies against other antigens.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALIPRANDINI, Eduardo. Anti-tetanus human monoclonal antibodies.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.