TY - JOUR
T1 - Immunotherapy Using Immunogenic Mimotopes Selected by Phage Display plus Amphotericin B Inducing a Therapeutic Response in Mice Infected with Leishmania amazonensis
AU - Soyer, Tauane G.
AU - Ramos, Fernanda F.
AU - Pereira, Isabela A.G.
AU - Lage, Daniela P.
AU - Bandeira, Raquel S.
AU - de Jesus, Marcelo M.
AU - Costa, Guilherme P.
AU - Machado, Amanda S.
AU - Freitas, Camila S.
AU - Vale, Danniele L.
AU - Martins, Vívian T.
AU - Galdino, Alexsandro S.
AU - Chávez-Fumagalli, Miguel A.
AU - Menezes-Souza, Daniel
AU - Duarte, Mariana C.
AU - Roatt, Bruno M.
AU - Coelho, Eduardo A.F.
AU - Tavares, Grasiele S.V.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - Leishmania amazonensis can cause cutaneous and visceral clinical manifestations of leishmaniasis in infected hosts. Once the treatment against disease is toxic, presents high cost, and/or there is the emergence of parasite-resistant strains, alternative means through which to control the disease must be developed. In this context, immunotherapeutics combining known drugs with immunogens could be applied to control infections and allow hosts to recover from the disease. In this study, immunotherapeutics protocols associating mimotopes selected by phage display and amphotericin B (AmpB) were evaluated in L. amazonensis-infected mice. Immunogens, A4 and A8 phages, were administered alone or associated with AmpB. Other animals received saline, AmpB, a wild-type phage (WTP), or WTP/AmpB as controls. Evaluations performed one and thirty days after the application of immunotherapeutics showed that the A4/AmpB and A8/AmpB combinations induced the most polarized Th1-type immune responses, which reflected in significant reductions in the lesion’s average diameter and in the parasite load in the infected tissue and distinct organs of the animals. In addition, the combination also reduced the drug toxicity, as compared to values found using it alone. In this context, preliminary data presented here suggest the potential to associate A4 and A8 phages with AmpB to be applied in future studies for treatment against leishmaniasis.
AB - Leishmania amazonensis can cause cutaneous and visceral clinical manifestations of leishmaniasis in infected hosts. Once the treatment against disease is toxic, presents high cost, and/or there is the emergence of parasite-resistant strains, alternative means through which to control the disease must be developed. In this context, immunotherapeutics combining known drugs with immunogens could be applied to control infections and allow hosts to recover from the disease. In this study, immunotherapeutics protocols associating mimotopes selected by phage display and amphotericin B (AmpB) were evaluated in L. amazonensis-infected mice. Immunogens, A4 and A8 phages, were administered alone or associated with AmpB. Other animals received saline, AmpB, a wild-type phage (WTP), or WTP/AmpB as controls. Evaluations performed one and thirty days after the application of immunotherapeutics showed that the A4/AmpB and A8/AmpB combinations induced the most polarized Th1-type immune responses, which reflected in significant reductions in the lesion’s average diameter and in the parasite load in the infected tissue and distinct organs of the animals. In addition, the combination also reduced the drug toxicity, as compared to values found using it alone. In this context, preliminary data presented here suggest the potential to associate A4 and A8 phages with AmpB to be applied in future studies for treatment against leishmaniasis.
KW - amphotericin B
KW - immune response
KW - immunotherapeutics
KW - mimotopes
KW - phage display
KW - tegumentary leishmaniasis
UR - http://www.scopus.com/inward/record.url?scp=85148766526&partnerID=8YFLogxK
U2 - 10.3390/pathogens12020314
DO - 10.3390/pathogens12020314
M3 - Article
AN - SCOPUS:85148766526
SN - 2076-0817
VL - 12
JO - Pathogens
JF - Pathogens
IS - 2
M1 - 314
ER -