Chimeric Protein IPath® with Chelating Activity Improves Atlantic Salmon’s Immunity against Infectious Diseases

Abstract

Infection processes displayed by pathogens require the acquisition of essential inorganic nutrients and trace elements from the host to survive and proliferate. Without a doubt, iron is a crucial trace metal for all living organisms and also a pivotal component in the host–parasite interactions. In particular, the host reduces the iron available to face the infectious disease, increasing iron transport proteins’ expression and activating the heme synthesis and degradation pathways. Moreover, recent findings have suggested that iron metabolism modulation in fish promotes the immune response by reducing cellular iron toxicity. We hypothesized that recombinant proteins related to iron metabolism could modulate the fish’s immune system through iron metabolism and iron-responsive genes. Here a chimeric iron transport protein (IPath®) was bioinformatically designed and then expressed in a recombinant bacterial system. The IPath® protein showed a significant chelating activity under in vitro conditions and biological activity. Taking this evidence, a vaccine candidate based on IPath® was evaluated in Atlantic salmon challenged with three different fish pathogens. Experimental trials were conducted using two fish groups: one immunized with IPath® and another injected with adjutant as the control group. After 400 accumulated thermal units (ATUs), two different infection trials were performed. In the first one, fish were infected with the bacterium Aeromonas salmonicida, and in a second trial, fish were exposed to the ectoparasite Caligus rogercresseyi and subsequently infected with the intracellular bacterium Piscirickettsia salmonis. Fish immunized with IPath® showed a significant delay in the mortality curve in response to A. salmonicida and P. salmonis infections. However, no significant differences between infected and control fish groups were observed at the end of the experiment. Notably, sea lice burden reduction was observed in vaccinated Atlantic salmon. Transcriptional analysis evidenced a high modulation of iron-homeostasis-related genes in fish vaccinated with IPath® compared to the control group during the infection. Moreover, increasing expression of Atlantic salmon IgT was associated with IPath® immunization. This study provides evidence that the IPath® protein could be used as an antigen or booster in commercial fish vaccines, improving the immune response against relevant pathogens for salmon aquaculture.

Exploring Sea Lice Vaccines against Early Stages of Infestation in Atlantic Salmon (Salmo salar)

“…Moreover, a chimeric antigen design from different iron-transporters sea lice proteins (IPath ® ) evidenced the modulation of iron homeostasis and immune response genes in S. salar . Moreover, the IPath ® vaccines showed a 95% efficacy in C. rogercresseyi burden reduction [ 41 , 79 ]. This study evaluated the effects of three vaccine prototypes in sea lice infestation.…”

“…Furthermore, changes in immunoglobulins expression were observed in vaccinated fish. Additionally, immunoglobulins expression increase has been reported in fish vaccinated with sea IPath ® vaccine and TT-P0 antigen [ 35 , 41 , 79 ]. It is possible to suggest the activation of Ig genes due to fish vaccination with the proposed prototypes.…”

“…The evaluation of vaccine prototypes against early sea louse infestation was conducted by seven immune response genes and seven iron regulation genes ( Table S1 ) in the skin and head kidney by RT-qPCR, according to Valenzuela-Muñoz et al [ 41 ]. Additionally, the reaction efficiency of each primer was calculated ( Table S1 ).…”

“…Notably, has been observed the expression modulation of IgM and IgT, antioxidant response, and related inflammatory genes in fish immunized and exposed to the ectoparasite infestation [ 37 , 39 , 40 ]. Moreover, the use of antigens associated with the host–iron metabolism modulation was recently reported [ 41 ]. Our recently published study demonstrated that the IPath ® vaccine, with chelating iron function, reported a sea lice burden reduction of over 90% [ 41 ].…”

“…Moreover, the use of antigens associated with the host–iron metabolism modulation was recently reported [ 41 ]. Our recently published study demonstrated that the IPath ® vaccine, with chelating iron function, reported a sea lice burden reduction of over 90% [ 41 ]. The findings suggested that identified antigens in marine ectoparasites trigger host humoral and cellular immune responses and activate host nutritional immunity during lice infestations [ 42 ].…”