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Comparison of the neutralizing activity and the glycosylation pattern of the IgG antibodies induced by pre-exposure schedule of human rabies vaccination

Grant number: 18/17580-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: December 01, 2018
End date: May 14, 2020
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Sandriana dos Ramos Silva
Grantee:Gabriela Koike
Host Institution: Instituto Pasteur (IP). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

According to the World Health Organization (WHO), rabies is responsible for about 55,000 deaths annually and to date, prophylaxis is the indicated measure for disease prevention. Currently rabies vaccines consist of inactivated viruses replicated in continuous cell lines, according to the WHO recommended protocol. In general, the immunological principle involved is the production of neutralizing IgG antibodies. Previous work has focused on the study of humoral response against rabies virus only in the quantitative aspect; however, the mechanism of how the specific antibodies neutralize the rabies virus is not fully understood yet. It is known that in addition to neutralization, antibodies mediate a variety of other important effector functions for pathogen elimination, which depends on the recruitment of cells of the innate immune system by means of receptors specific to the Fc region of the antibody. Furthermore, it is known that glycosylation of the antibody plays a key role in maintaining its conformational structure, effector functions and pharmacokinetics. Recently, it has been shown that immunization is capable of inducing production of specific antibodies with similar glycosylation pattern, suggesting that the glycosylation process is not only programmed, but can be manipulated by different inflammatory signals during the activation of B cell. Based on that, the aim of the present study is to compare the neutralizing activity with the glycosylation profile of the specific IgG antibodies after vaccination scheme of pre-exposure to human rabies. We expect to contribute with information about the functional quality of the neutralizing antibodies obtained after vaccination scheme, which may be relevant for the development of new biotechnological compounds with therapeutic application.

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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)
KOIKE, GABRIELA; KATZ, IANA SULY SANTOS; FERNANDES, ELAINE RANIERO; GUEDES, FERNANDA; SILVA, SANDRIANA RAMOS. Glycosylation is required for the neutralizing activity of human IgG1 antibodies against human rabies induced by pre-exposure prophylaxis. Immunobiology, v. 226, n. 2, . (18/17580-3)