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

2020; Multidisciplinary Digital Publishing Institute; Volume: 8; Issue: 4 Linguagem: Inglês

10.3390/vaccines8040565

2076-393X

Lennon Ramos Pereira, Elaine Cristina Matos Vicentin, Sara Araújo Pereira, Denicar Lina Nascimento Fabris Maeda, Rúbens Prince dos Santos Alves, Robert Andreata‐Santos, Francielle Tramontini Gomes de Sousa, Márcio Yamamoto, Maria Fernanda de Castro‐Amarante, Marianna Teixeira de Pinho Favaro, Camila Malta Romano, Éster Cerdeira Sabino, Silvia Beatriz Boscardin, Luís Carlos de Souza Ferreira,

Mosquito-borne diseases and control

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 αDEC205 or αDCIR2 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 αDEC205 or αDCIR2 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.