Engineering of VHHs monoclonal antibodies against Bothrops snake serinoproteases

• Grant number: 22/15800-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2023
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Sonia Aparecida de Andrade Chudzinski
• Grantee: Daniel Alexandre de Souza
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil

Abstract

Snakebite is a public health problem that affects more than 2 million people every year, mostly peripheral and rural populations of working age, and who live in places with difficult access to treatment. In 2017, the World Health Organization added snakebite accidents to category A of neglected tropical diseases, the highest in the class, and set the goal of reducing snakebite burden by 50% by 2030. In Brazil, more than 20,000 cases are reported annually, 85% of which are attributed to snakes of the genus Bothrops. Bothrops venom is a highly complex mixture of proteins, peptides and enzymes that act synergistically and trigger a variety of local symptoms, such as hemorrhage, edema and ecchymosis, which can lead to necrosis and limb amputation; and systemic, such as coagulopathies and thrombocytopenia. The treatment for envenoming indicated by the Ministry of Health is the administration of antivenom from the immunization of horses, which despite being highly effective in preventing lethality, still has limitations such as partial neutralization of serineproteases and low immunochemical purity. With this in mind, a worldwide trend in the fight against ophidism is the development of new-generation antivenoms, based on recombinant monoclonal antibodies that neutralize the main toxins present in the venom. And in this context, VHHs or nanobodies have a set of desirable characteristics for the development of recombinant antivenoms. With this in mind, this work aims to develop VHHs anti-serineprotease from the venom of Bothrops snakes, being the first step in the production of a recombinant Bothropic antivenom based on monoclonal antibodies.