TYPES OF FISH VACCINES AND THEIR EFFICACIES

Signal 1 Facilitators and Signal 2 Facilitators, Their Immunomodulatory Compounds, Receptors They Act on and Principal Immune Responses They Elicit

10.3 TYPES OF FISH VACCINES AND THEIR EFFICACIES

Vaccine research has become a critical tool for preventing diseases in farmed fish (4). Vaccines come in a variety of forms, including inactivated vaccines, live attenuated vaccines, DNA vaccines, and subunit vaccines (16).

10.3.1 I^nactIVated w^Hole-c^ell V^accInes

For many years, inactivated whole-cell vaccines have been widely utilized, and they have been shown to be effective against bacterial infections in fish (5). The most extensively used and commer- cially manufactured vaccines for controlling diseases in aquaculture are formalin-inactivated vac- cines. The vaccine against enteric red mouth (ERM) disease, which consists of killed whole cells, was initially licensed and commercialized in the late 1970s (17). The safety of formalin treatment, which is a dependable and inexpensive technique for killing pathogens, is an advantage of inacti- vated bacterial vaccinations (4). However, if injected, this form of vaccine may require an adjuvant to elicit an appropriate long-term immune response while, if administered through the mucosal route, it may require booster immunization (13–18). Despite promoting a specific immune response against a pathogen, these vaccinations do not mount a response specific to a target, but many epit- opes. Thus, even though the immune system of the fish can build memory cells against the disease, it may not be as effective as a live attenuated vaccine or a DNA vaccine. These fish vaccinations are currently available in North America, Chile, Japan, Australia, and Europe (5,19). Examples of suc- cessful inactivated whole-cell vaccines and their efficacies in aquaculture are listed in Table 10.4.

10.3.2 l^IVe a^ttenuated V^accInes

Several live attenuated vaccines against bacterial diseases have recently been produced (20–22).

They have been shown to be more effective than inactivated whole-cell vaccines at eliciting a pro- tective immune response, with more persistent memory responses, greater survival rates, and more robust cellular and humoral immune responses (23). Unlike inactivated vaccines, a live attenuated vaccine can still undergo some replication in vivo, triggering the immune responses in a manner similar to that of a natural infection, but not properly expressing the virulence factors (4). Although attenuated live vaccines can induce an effective immune response, they may pose a danger of reverting to a virulent phenotype (4); however, it has been proven that live attenuated vaccines are an effective strategy against bacterial infectious diseases. Table 10.4 lists a number of successful examples of their use in aquaculture.

10.3.3 deoxyrIBonucleIc a^cId (dna) V^accInes

DNA vaccines have recently been produced and are a viable alternative to whole-cell immunizations (24,25). DNA vaccines are composed of a strong promoter expression plasmid, the gene of interest, and a polyadenylation/transcriptional termination sequence. This vaccine is given to the host as puri- fied plasmid DNA, and the expression of the encoded protein(s) is induced in the host cells, resulting in strong and long-lasting immunity (1,26). DNA vaccines have been shown, in a number of trials,

158 Fish Vaccines to elicit robust innate and adaptive immunity (27–29). They have been developed for several fish species, to promote immunity against bacterial and viral diseases (5). DNA vaccines may be more effective in the production of immune responses against viral pathogens, as the antigen(s) are formed intracellularly and likely presented by the MHC I presentation pathway, which is comparable to the reaction during viral infections (4). Recent research has shown that the antigen type, vaccine dose, and duration of expression have an impact on the generated immune responses and vaccine efficacy (1). Table 10.4 details a number of successful instances of DNA vaccine applications in aquaculture.

10.3.4 s^uBunIt V^accInes

The development of subunit vaccines for aquaculture has been made possible by advancements in molecular biology and genetic engineering. They are primarily recombinant proteins used as purified antigens, and rely on the identification of vaccine candidates that can elicit specific protec- tive immunity against the disease in question (30). Subunit vaccines are safer than conventional vaccines in experimental animals (i.e., inactivated whole-cell or live attenuated vaccines) (31).

However, despite their effectiveness in preventing diseases, subunit vaccines have several limita- tions, including their high cost of production and the fact that, as single pure proteins, they typically lack self-adjuvant ability, produce short-lived immune responses, and have poor immunogenicity (32,33). They have, however, been demonstrated to generate long-lasting immune responses against diseases when given regularly over a period of time (34,35). Table 10.4 provides a number of suc- cessful instances of subunit vaccine usage in aquaculture.

TABLE 10.4

Examples of Fish Vaccines

Pathogens Fish Species

Administration Method

Efficacy as Relative Percent

Survival (RPS) Remark References Inactivated vaccines

Salmonid alphavirus Vibrio

anguillarum A novel

hydrogen peroxide- inactivated vaccine

Inactivated vaccine based on a strain of SAV subtype 3-ALV405

Turbot, Scophthalmus maximus Nile tilapia, Oreochromis

niloticus

i.p. injection

i.p. injection i.p. injection

98.5%

90%

59.3%

Protection against SAV-induced mortality Induce specific antibodies Induce specific antibodies

(36) (37) (37)

Live attenuate vaccines Aeromonas

hydrophila

Edwardsiella spp.

Common carp, Cyprinus carpio Zebrafish, Danio rerio

Turbot, Scophthalmus maximus

i.p. injection

immersion

37–83%

70–100%

83–89%

Induction of serum- specific IgM and upregulation of immune-related genes after vaccination The novel vaccine

manifested satisfactory immune protection on turbot

(38) (39)

(40)

(Continued)

Safety and Efficacy of Vaccines in Aquaculture 159

TABLE 10.4 (continued) Examples of Fish Vaccines

Pathogens Fish Species

Administration Method

Efficacy as Relative Percent

Survival (RPS) Remark References E. ictaluri

E. piscicida

Channel catfish, I. punctatus, Hybrid catfish, I. punctatus × I.

furcatus

Oral 85-88% Cross-protection of live attenuated E. ictaluri vaccine against E.

piscicida

(41)

DNA vaccines Vibrio

anguillarum

Nocardia spp.

Flounder, Paralichthys olivaceus

Hybrid snakehead

i.m. injection

i.m. injection

50%

79.33%

Induction of the T lymphocyte response, followed by B lymphocyte induction of specific antibodies DNA vaccine show

protection against N.

seriolae infection

(42)

(43)

Subunit vaccines Edwardsiella

ictaluri

Infectious spleen and kidney necrosis virus

Nile tilapia, Oreochromis niloticus

Mandarin fish, Siniperca chuatsi

i.p. injection

immersion

42%

86.7%

Antigenicity of the chimeric protein was exhibited by strong reactivity with serum Induction of the immune

protective effect of naked subunit vaccine

(30)

(34)

Aeromonas hydrophila

S. agalactiae

A. salmonicida

V. harveyi

Rainbow trout, Oncorhynchus mykiss

Nile tilapia, Oreochromis niloticus

Rainbow trout, O. mykiss

Golden pompano, Trachinotus ovatus

immersion and i.p. injection

i.p. injection

i.p. injection

i.p. injection

21.56–78.88%

80–93%

46–86%

52.39%

A. hydrophila glycoproteins with Al(OH)₃ and ginseng could be used as a safe and effective vaccine for fish Ghost vaccine can

enhance cellular and humoral immune responses and show high

immunoprotection High survival post-

vaccination and a few novel candidate proteins, and the survival can be linked to the antibody- producing protective qualities.

Fish had both innate and adaptive immune responses

(44)

(45)

(33)

(32)

160 Fish Vaccines

10.4 ADJUVANTS FOR FISH VACCINES AND THE PROTECTIVE EFFICACIES