Work in progress

Vaccine ‘work in progress’ in major aquaculture markets, Part 1: Sea bass

The scientific journal Vaccines recently published a review of “the most significant and innovative vaccine research” in three economically important fish species: European sea bass, Nile tilapia and Atlantic salmon. In this three-part series, the editors of Fish Health Forum summarize the main findings for each species.

European sea bass aquaculture is centered on the Mediterranean basin, and there are a number of notable pathogens which can cause high mortality on production sites through direct and indirect effects. To date, vaccine research has focused on bacterial and viral pathogens of sea bass, the authors explained.

Boosters, inactivation methods scrutinized

There have been recent moves to develop a vaccine against Mycobacterium marinum, the causative agent of mycobacteriosis, a chronic bacterial disease causing multiple symptoms in fish, the scientists said. Studies have used an avirulent strain for the vaccine, M. marinum iipA::ka, delivered by intraperitoneal (IP) injection, with a challenge with the virulent strain M. marinum Eilat.

One study cited by the authors used a booster vaccination, which increased mortality and infection rates significantly, despite increasing antibody titers.

“This demonstrates how antibody response alone is not, by itself, necessarily indicative of the vaccine effectiveness,” they stressed.

The researchers also commented on methods of vaccine inactivation, noting that in two pieces of similar research, granulomatous lesions were observed after vaccination but prior to challenge.

“Heat inactivation does not appear to be a viable technique for the production of vaccines against mycobacteriosis, at least when the iipA::kan mutant is used as strain, because of its side effects,” they concluded.

Combination of approaches may prove useful

Studies exploring possible vaccines against Tenacibaculum maritimum, which causes the ulcerative condition tenacibaculosis, using different antigens were reviewed. Those using formalin-killed cells and extracellular products saw significantly increased survival rates, the scientists said.

“Because antigens in the two formulations likely differ from one another, we hypothesize that their simultaneous administration could yield better results by inducing a more complete protection. This may lead to a formulation similar to that described against Streptococcus iniae for Nile tilapia, where the vaccine had been obtained by resuspending formalin-inactivated cells in a concentrated medium rich in extracellular products,” they suggested.

Adjuvants bring increased effectiveness

A commercial oral vaccine against Vibrio anguillarum and V. ordalii has seen improved effectiveness through the addition of recombinant sea bass tumor necrosis factor α as an adjuvant, the authors reported. Over three challenges at 30, 85 and 118 days after a booster, increased survival rates with the adjuvanted vaccine described as “impressive” were observed.

“This supports the key role of adjuvants and highlights the role of protein biotechnologies in implementing the field of animal health. Interestingly, disease resistance was not correlated to titers, as both vaccinated groups displayed a slight increase in specific IgM against serotypes,” they said.

The importance of adjuvants was further demonstrated in a study comparing the performance of adjuvanted and unadjuvanted vaccines against V. anguillarum and Photobacterium damselae subsp. piscicida, with the adjuvanted product offering better protection against vibriosis in four out of five trials.

Viral pathogens in focus

The main focus of vaccine research against viral pathogens affecting sea bass to date has been on the Betanodavirus genus, known as nervous necrosis virus (NNV) or (VERv), the authors explained.

One study explored three different methods of inactivating the highly pathogenic red-spotted grouper nervous necrosis virus (RGNNV), as well as delivery by IP injection and immersion. Formalin- and heat-inactivated vaccines were most effective in eliciting an immune response, the researcher said, and only those vaccinated by injection saw significantly lower mortality.

Another RGNNV study used ultra violet as an inactivation method. This approach “would be advantageous in terms of convenience, cost and safety,” suggested the authors. Specific antiviral and antibody response was noted in the research, but questions remain over the vaccine’s pathway of action, they added.

Multiple genotypes pose vaccine challenge

Cross-protection against RGNNV and another, less pathogenic genotype of the same virus, striped Jack nervous necrosis virus (SJNNV), is sought by researchers. A study found that a formalin-inactivated RGNNV vaccine performed better than an SJNNV equivalent, the scientists noted, with the highest titers and neutralizing activity against antigens.

“Inactivated vaccines against VERv appear to be partially effective in protecting animals from lethal challenges when administered intraperitoneally,” they concluded.

“It is plausible that adjuvants may confer some improvements to the above-mentioned vaccines. Furthermore, a multi-strain vaccine formulation containing the most harmful strains affecting European sea bass could help achieve a broader protection.”

Recombinant vaccines may prove practical

Research on recombinant vaccines against NNV was also discussed.

One study used whole cultures of Escherichia coli and saw higher titers and antibody response using IP injection than oral administration, though was inconclusive on mortality effects, the authors suggested. Another used viral-like particles (VLPs) of NNV expressed in the plant Nicotiana benthamiana or integrated into tobacco cells, with significantly reduced mortality compared to controls.

“VLP-based vaccines have not entered the market yet but appear potentially attractive against Betanodavirus due to the results elicited and their operational safety: neither are they replication-capable (they do not contain any viral genetic material) nor do they require the use of live virus during the production stages,” they explained.

“From a legislative perspective, this may simplify the regulation and approval processes. A similar strategy may also be employed for producing vaccines against further viral pathologies.”

To view the full review in Vaccines, click here.