Analysis of the polyclonal antibody response elicited after influenza a virus infection and immunization

• Grant number: 19/20772-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Rebeca de Paiva Froes Rocha
• Supervisor: Andrew Barrett Ward
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Scripps Research Institute, San Diego, United States
• Associated to the scholarship: 18/02594-9 - Development of a model of Usutu virus infection in mice: study of disease and testing of a neuroprotective compound, BP.DR

Abstract

The adaptive immune response has evolved to recognize, eliminate, and remember pathogens. However, influenza A viruses (IAV) have co-evolved to circumvent adaptive immune recognition. Despite our best efforts, there is still an unmet need for better comprehension of how the immune response targets IAV and how IAV evades antibody (Ab) recognition on acute and extended timelines. This knowledge is imperative for understanding how to train the adaptive immune system to control IAV infection, providing a necessary foundation for developing a universal influenza vaccine. It is difficult to obtain a comprehensive understanding of the polyclonal immune response to IAV vaccination and infection, such as the dynamics of strain-specific or cross-protective responses and the role of recall in steering immune responses. Recent technological advances produce a more extensive picture of humoral immunity to IAV, yet current techniques cannot discern the full complexity of polyclonal Ab (pAb) responses, and the processes are labor-intensive and time-consuming. Single particle electron microscopy powerfully distinguishes detail in heterogenous samples, providing the sensitivity necessary to thoroughly characterize the pAb response to IAV vaccination and infection. We therefore propose to map the dynamics of the pAb response to IAV after vaccination, applying our novel imaging strategy to decipher polyclonal immune responses by EM polyclonal epitope mapping, successfully established by the Ward lab. Via collaboration we have acquired human sera samples from different cohorts of infected or vaccinated individuals that will serve as the basis for these studies. In particular we would like to understand how pre-existing immunity to an epitope or epitopes effects de novo responses as well as probe the cross-reactive antibodies within an individual. These data will enable rational design of immunogens intended to elicit improved antibody responses, which can be tested in animal models (e.g. mouse) and eventually translated into humans. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FONTOURA, MARINA ALVES; ROCHA, REBECA FROES; MARQUES, RAFAEL ELIAS. Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection. LIFE-BASEL, v. 11, n. 7, JUL 2021. (18/02594-9, 18/10990-1, 19/20772-4)