MANα1‐2MAN decorated liposomes enhance the immunogenicity induced by a DNA vaccine against BoHV‐1

KORNUTA, CLAUDIA A.; BIDART, JUAN E.; SORIA, IVANA; GAMMELLA, MARIELA; QUATTROCCHI, VALERIA; PAPPALARDO, JUAN S.; SALMASO, STEFANO; TORCHILIN, VLADIMIR P.; CHEUQUEPÁN VALENZUELA, FELIPE; HECKER, YANINA P.; MOORE, DADIN P.; ZAMORANO, PATRICIA I.; LANGELLOTTI, CECILIA A.

TRANSBOUNDARY AND EMERGING DISEASES

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020

1865-1674

New technologies in the field of vaccinology arise as a necessity for the treatmentand control of many diseases. Whole virus inactivated vaccines and modified livevirus ones used against Bovine Herpesvirus-1 (BoHV-1) infection have several disadvantages. Previous works on DNA vaccines against BoHV-1 have demonstratedthe capability to induce humoral and cellular immune responses. Nevertheless,?naked? DNA induces low immunogenic response. Thus, loading of antigen encodingDNA sequences in liposomal formulations targeting dendritic cell receptors couldbe a promising strategy to better activate these antigen-presenting cells (APC). Inthis work, a DNA-based vaccine encoding the truncated version of BoHV-1 glycoprotein D (pCIgD) was evaluated alone and encapsulated in a liposomal formulationcontaining LPS and decorated with MANα1-2MAN-PEG-DOPE (pCIgD-Man-L). Thevaccinations were performed in mice and bovines. The results showed that the useof pCIgD-Man-L enhanced the immune response in both animal models. For humoral immunity, significant differences were achieved when total antibody titresand isotypes were assayed in sera. Regarding cellular immunity, a significant increasein the proliferative response against BoHV-1 was detected in animals vaccinatedwith pCIgD-Man-L when compared to the response induced in animals vaccinatedwith pCIgD. In addition, upregulation of CD40 molecules on the surface of bovinedendritic cells (DCs) was observed when cells were stimulated and activated withthe vaccine formulations. When viral challenge was performed, bovines vaccinatedwith MANα1-2MAN-PEG-DOPE elicited better protection which was evidenced bya lower viral excretion. These results demonstrate that the dendritic cell targetingusing MANα1-2MAN decorated liposomes can boost the immunogenicity resultingin a long-lasting immunity. Liposomes decorated with MANα1-2MAN-PEG-DOPEwere tested for the first time as a DNA vaccine nanovehicle in cattle as a preventivetreatment against BoHV-1. These results open new perspectives for the design ofvaccines for the control of bovine rhinotracheitis.