Alternatives to mineral oil adjuvants in vaccines against Aeromonas salmonicida subsp. salmonicida in rainbow trout offer reductions in adverse effects

Kasper Rømer Villumsen,Anders Miki Bojesen,Dennis Christensen,Erling Olaf Koppang

doi:10.1038/s41598-017-06324-7

Abstract

In an effort to reduce the frequency and severity of adverse reactions seen from the use of mineral oil adjuvants in salmonid fish, the effects of two alternative adjuvants were assessed, focusing on the induction of adverse effects as well as protection. Using rainbow trout (Oncorhynchus mykiss) as recipients, injection vaccines based on formalin-inactivated Aeromonas salmonicida subspecies salmonicida were formulated with CpG oligodeoxynucleotides, the liposomal cationic adjuvant formulation 01 (CAF01) or with Freund’s incomplete adjuvant and administered intraperitoneally. Control groups of unvaccinated, Tris-buffered saline-injected or bacterin-injected individuals were included, and each group included in the study held a total number of 240 individuals. Subsequently, individuals from each group were examined for differences in Fulton’s condition factor, macro- and microscopic pathological changes, as well as protection against experimental infection with A. salmonicida. While adverse effects were not eliminated, reductions in microscopic and macroscopic adverse effects, in particular, were seen for both the nucleotide- and liposome-based vaccine formulations. Furthermore, the induced protection appears similar to that of the benchmark formulation, thus introducing viable, potential alternative types of adjuvants for use in future fish vaccines.

Highlights

Intensive, modern aquaculture production depends on successful prophylactic control of and treatment against a variety of waterborne viral, parasitic, as well as bacterial pathogens
In order to examine potential alternatives to mineral oil-adjuvanted vaccine formulations according to the criteria stated in the introduction, the in vivo performance of three experimental furunculosis vaccine formulations was assessed in rainbow trout
Vaccine formulations utilizing aluminum salt and mineral oil adjuvants have been connected with growth reduction in Atlantic salmon[7, 30, 31]

Summary

Introduction

Modern aquaculture production depends on successful prophylactic control of and treatment against a variety of waterborne viral, parasitic, as well as bacterial pathogens. Current prophylactic strategies rely primarily on intraperitoneal injection of vaccines formulated with mineral oil adjuvants This strategy has successfully induced long-term protection[1,2,3,4,5], a variety of adverse effects, including adhesions and pigmentation of the peritoneal viscera, growth reduction[2, 3, 5, 6], deformed vertebrae[7], autoimmunity and hypergammaglobulinemia[8, 9] have been observed. Freund’s incomplete adjuvant was included to serve as a benchmark formulation, based in part on its chemical composition of mineral oil and surfactant that resembles that of commercially available vaccines, and on previous experiences with induction of both protection and adverse effects with this formulation in rainbow trout[4, 5]. The water-in-oil characteristics of FIA emulsions, are thought to contribute to a depot-effect through which antigen is released slowly over time, and to contribute to increased uptake by phagocytic cells[20]

Methods

Results

Conclusion