Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1

Author(s):Show less -

Pereira, Lennon Ramos ^[1] ; Vicentin, Elaine Cristina Matos ^[2] ; Pereira, Sara Araujo ^[1] ; Maeda, Denicar Lina Nascimento Fabris ^[1] ; Alves, Rubens Prince dos Santos ^[1] ; Andreata-Santos, Robert ^[1] ; Sousa, Francielle Tramontini Gomes de ^[3] ; Yamamoto, Marcio Massao ^[2] ; Castro-Amarante, Maria Fernanda ^[1] ; Favaro, Marianna Teixeira de Pinho ^[1] ; Romano, Camila Malta ^[3] ; Sabino, Ester Cerdeira ^[3] ; Boscardin, Silvia Beatriz ^[2] ; Ferreira, Luis Carlos de Souza ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Clin Hosp HCFMUSP, Fac Med, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: VACCINES; v. 8, n. 4 DEC 2020.
• Web of Science Citations: 0

Abstract

Targeting dendritic cells (DCs) by means of monoclonal antibodies (mAbs) capable of binding their surface receptors (DEC205 and DCIR2) has previously been shown to enhance the immunogenicity of genetically fused antigens. This approach has been repeatedly demonstrated to enhance the induced immune responses to passenger antigens and thus represents a promising therapeutic and/or prophylactic strategy against different infectious diseases. Additionally, under experimental conditions, chimeric alpha DEC205 or alpha DCIR2 mAbs are usually administered via an intraperitoneal (i.p.) route, which is not reproducible in clinical settings. In this study, we characterized the delivery of chimeric alpha DEC205 or alpha DCIR2 mAbs via an intradermal (i.d.) route, compared the elicited humoral immune responses, and evaluated the safety of this potential immunization strategy under preclinical conditions. As a model antigen, we used type 2 dengue virus (DENV2) nonstructural protein 1 (NS1). The results show that the administration of chimeric DC-targeting mAbs via the i.d. route induced humoral immune responses to the passenger antigen equivalent or superior to those elicited by i.p. immunization with no toxic effects to the animals. Collectively, these results clearly indicate that i.d. administration of DC-targeting chimeric mAbs presents promising approaches for the development of subunit vaccines, particularly against DENV and other flaviviruses. (AU)

• FAPESP's process: 13/26942-2 - Development of a vaccine formulation against dengue based on the nonstructural protein 1 (NS1) administered by the intradermal route
• Grantee: Lennon Ramos Pereira
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 14/04303-0 - Identification of epitopes present in the e protein of dengue virus type 2 (DENV2) capable of generating neutralizing antibodies without causing exacerbation of viral replication
• Grantee: Denicar Lina Nascimento Fabris
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/05570-8 - Use of Zika virus recombinant proteins for development of diagnostic methods and vaccines
• Grantee: Lennon Ramos Pereira
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/01702-9 - Evaluation of endothelial permeability to study dengue pathogenesis and screen compounds with therapeutic potential
• Grantee: Francielle Tramontini Gomes de Sousa
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/11442-4 - Study of protective mechanisms induced by vaccination of mice with fusion antibodies that target the dengue virus proteins to dendritic cells
• Grantee: Silvia Beatriz Boscardin
• Support type: Regular Research Grants
• FAPESP's process: 14/17595-0 - New vaccine research based on recombinant proteins of dengue virus
• Grantee: Luis Carlos de Souza Ferreira
• Support type: Regular Research Grants
• FAPESP's process: 13/01690-0 - Establishment of an in vitro model of vascular permeability evaluation to study the hemorrhagic dengue fever pathogenesis and screening of compounds with therapeutic potential
• Grantee: Ester Cerdeira Sabino
• Support type: Regular Research Grants