Improving fish health and the aquatic environment through vaccination
Submitting InstitutionUniversity of Stirling
Unit of AssessmentAgriculture, Veterinary and Food Science
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Medical Microbiology
Summary of the impact
Research by the Institute of Aquaculture has made a significant
contribution to the development of effective fish vaccines, some of which
have been commercialised and are used widely within the aquaculture
industry. The majority of farmed fish in the UK are vaccinated (44 million
salmon and 7.5 million rainbow trout in 2012 alone) with vaccines
developed at Stirling, resulting in vast improvements in survival and fish
health, and a sustained minimal use in antibiotics through mass
vaccination. Vaccines have been developed for all the major farmed species
in Europe, and recently the first vaccine for Pangasius catfish in
Vietnam (>2 million tonne).
While aquaculture is rapidly expanding worldwide the single most
important limiting factor on continued growth is loss due to disease. In
some sectors of the aquaculture industry disease losses can reach up to
40% of a fish population, threatening the very existence of certain
sectors. Prior to the introduction of vaccines, antibiotics were the only
method of controlling bacterial diseases.
Fish immunology research at the Institute of Aquaculture has contributed
essential tools and methods to assist in the development of fish vaccines
since 1993. The group has close links with industry and much of the
research has been undertaken with funding from major pharmaceutical
companies, leading to commercialisation of the vaccines developed
(Furunculosis, Pasteurellosis, Bacillary Necrosis).
In order to develop an effective vaccine the protective antigens need to
be identified and their protective response confirmed in the host species.
As very few reagents were available to monitor the immune response or to
identify pathogens in fish, this became one of the main tasks for the
group at Stirling (1993-date) and a wide range of monoclonal antibodies
(mAbs) and standard operating procedures were developed for this purpose1.The
fish health group has also made significant contributions to the
elucidation of host-pathogen interactions and characterisation of
pathogens for a number of fish species and diseases leading to vaccine
development e.g. Furunculosis 2 in salmonids,
Pasteurellosis3,4 in sea bass and sea bream, Aeromonad
septicaemia in carp and Tilapia 5, and Bacillary Necrosis in Pangasius
Development of methods to identify the antigens expressed by pathogens
during infection was also important so that potential vaccine candidates
could be isolated and tested. The team focused on differential expression
of pathogen antigens under different culture conditions leading to the
successful development of vaccines. This was first approached in 1995
using iron restriction conditions to culture Aeromonas salmonicida in
vitro2 and a vaccine to protect against
Furunculosis was subsequently developed. A similar approach was used to
develop a Pasteurellosis vaccine for use in Mediterranean fish species
(1997-2003)3,4. Aeromonas hydrophila is very
heterogeneous and therefore vaccine development was particularly
difficult, so more recently the team took a different approach in that the
bacteria were actually cultured in vivo in culture chambers rather
than manipulating the in vitro culture media. In addition,
immunoproteomics was used to identify common vaccine antigens between the
field isolates. This time a recombinant vaccine was successfully developed
(2005-2010)5. Finally, the first commercial fish vaccine for
use in Pangasius catfish was recently developed. This vaccine
protects against bacterial necrosis from Edwardsiella ictaluri
which is the most significant disease affecting the catfish sector in
Asia. The research performed at Stirling (2006-2011) provided the original
disease diagnosis, pathogen identification and screening of vaccine
candidates6. This is an extremely important development as the
use of antibiotics in Vietnamese aquaculture has been a cause for concern.
Key staff working on vaccine development include Adams (1995-present),
Thompson (1993- present), Richards (1979-present) and Crumlish
References to the research
The results of the research have been published widely in scientific
papers and disseminated in numerous trade magazines and through many oral
and poster presentations at scientific conferences.
1. Adams A, Thompson K D (2006) Biotechnology offers revolution to fish
health management. Trends in Biotechnology 24, 201-205.
2. Neelam, B., Thompson, K.D., Price, N.C., Tatner, M.F., Adams, A.,
Ellis, A.E. and Stevens, L. (1995) Development of monoclonal antibodies to
iron-regulated outer membrane proteins and lipopolysaccharide of Aeromonas
salmonicida. Diseases of Aquatic Organisms, 21, 201-208.
3. Bakopoulos, V., Adams, A. and Richards, R.H. (1997) The effect of iron
limitation growth conditions on the cell and extracellular components of
the fish pathogen Pasteurella piscicida. Journal of Fish
Diseases, 20, 297-305.
4. Bakopoulos V., Pearson M., Volpatti D., Gousmani L., Adams A.,
Galeotti M, Richards R.H. and Dimitriadis G.J. (2002) Investigation of
media formulations promoting differential antigen expression by Photobacterium
damsela ssp. piscicida and recognition by sea bass, Dicentrarchus
labrax (L.), immune sera. Journal of Fish Diseases 26, 1-13.
5. Poobalane S, Kim D. Thompson, László Ardó, Noel Verjan, Hyun-Ja Han,
Galina Jeney, Ikuo Hirono, Takashi Aoki, Alexandra Adams (2010) Production
and efficacy of an Aeromonas hydrophila recombinant S-layer
protein vaccine for fish. Vaccine 28, 3540-3547.
6. Crumlish, M., Thanh P.C., Koesling J., Tung, V.T and Gravningen K.
(2010) Experimental challenge studies in Vietnamese catfish Pangasianodon
hypophthalmus (Sauvage), exposed to Edwardsiella ictaluri
and Aeromonas hydrophila. Journal of Fish Diseases 33,
Grants supporting the underpinning research include:
1. 1998-2002: FAIR/EU - Fish Pasteurellosis vaccine development.
£424k, (PI Adams)
2. 1998: Aquaculture Vaccines Ltd - Aeromonas hydrophila
vaccine development. £21k, (PI Adams)
3. 2006: Schering Plough Aquaculture, Aeromonas hydrophila
vaccine development. £35k, (PI Adams/Thompson)
4. 2006-2011 Pharmaq Norway: Vaccine development against E. ictaluri
in farmed Pangasius species. £280k (PI Crumlish).
5. 2009-2010 Intervet Schering Plough Developing control strategies for Aeromonas
hydrophila. £40k (PI Adams/Thompson)
Details of the impact
Fish health and welfare
The vaccines developed and commercialised were to protect salmonids
against Furunculosis, sea bass/bream against Pasteurellosis, catfish
against Edwardsiella ictaluri and carp against Aeromonas
hydrophila. Field trials have been performed for the latter and
patents filed in the US (12/678,078) and Europe (008806225.2). Impact is
coroborated by Professor Patrick Smith, founder of the first fish vaccine
company (Aquaculture Vaccine Limited) `University of Stirling has a
pivotal role in the area of aquatic animal health research and its work
over the years has had a major impact on the worldwide aquaculture
industry which is so crucial for future world Food Security programmes'.
Use of vaccines led to a dramatic reduction in use of antibiotics in the
late 80s and this has been sustained to the present day with continued
wide-spread use of vaccines in UK and Norway. Thus, the use of antibiotics
in the salmonid aquaculture industry is very low in comparison to use in
other farmed animals. Impact on the aquatic environment is again
corroborated by Professor Patrick Smith `....antibiotic usage in
fish farms declined rapidly to the position we are at today where
Norwegian farmed salmon production has reached approximately 800,000
tonnes (a near 7-fold increase) while the usage of antibiotic has declined
to less than 100kg (a near 50-fold reduction)!'.
New fish vaccines have been developed and commercialised - this includes
vaccines to prevent Furunculosis, Pasteurellosis with 51.5 million doses
administered in 2012 (>£5m). The Strategic Marketing Director of MSD
Animal Health confirms `the key role which research and testing
undertaken by the Institute of Aquaculture at University of Stirling has
played in the development of vaccines.......I and my team are directly
involved in commissioning this work for the company'.
The first commercial fish vaccine against Bacillary Necrosis for use in Panagasius
catfish was launched in October 2011 by Pharmaq. ALPHA JECT Panga 1 was
granted a license in Vietnam in April 2013. Vaccination and training in
good practice in the vaccination process has been initiated.
Antibodies to fish immunoglobulins have been marketed through Aquatic
Diagnostics Ltd. Impact is confirmed by Professor Brian Dixon, University
of Waterloo, Canada `Indeed, antibodies to fish immunoglobulins for
various species are one commercial product that has emerged from this
line of research, with companies such as Aquatic Diagnostics in
Stirling, Scotland, marketing these.'
Industry has invested in research and development. Schering Plough
Aquaculture, now MSD Animal Health, have provided >£500,000 in funding
on fish vaccines (1998-2009), while Pharmaq has invested £280,000
(2006-11). Recently we were awarded £1,390,000 by Zoetis
(Pfizer)/Technology Strategy Board to develop a sea louse vaccine.
The position of contributing scientists on key committees and working
groups has ensured transfer of the knowledge generated to industry and
government and has influenced public policy. For example, Richards is the
veterinary advisor to the Scottish Salmon Producers Organisation and
chairs the Scottish Government Ministerial Group on Sustainable
Aquaculture Working Group on Fish Health. Adams is a member of the
Asia-Europe Meeting (ASEM) Aquaculture Health Steering Group, a
multi-stakeholder platform for networking and coordination concerning
sustainable aquaculture between EU and Asia. She has also recently joined
the Veterinary Medicines Directorate (VMD) Aquaculture Working Group on
control of antibiotic use. Richards and Adams are also facilitator and
immunology group leader of the European Aquaculture Technology and
Innovation Platform (EATIP) for Fish Health, which sets priorities for
commercially-focused research in aquaculture.
Introduction of the first fish vaccine in Vietnam has benefited fish
health, changed methods of fish husbandry in Vietnam, reduced the use of
antibiotics, and has benefited local people though creation of jobs and
wealth through increased productivity. Numerous workshops have been
conducted in disease diagnosis, microbiology, immunology and vaccine
development for a wide range of end-users including the scientific
community and farmers in a variety of countries including Chile, China,
Korea, Thailand and Vietnam. For example, in Vietnam workshops (translated
into Vietnamese and other languages) were given to 1,400 fish farmers and
a diagnostic facility and wet lab were established.
Sources to corroborate the impact
- Patents lodged in Europe (008806225.2) and USA (12/678,078) for A.
- First fish vaccine in Vietnam; www.pharmaq.no/updates/the-first-/
- Evidence that new antibodies to fish immunoglobulins for various
species have been developed:
University of Stirling spin-out company marketing antibodies developed
within the University.
In addition, letters corroborating the impact are available from MSD
Animal Health, Aquatic Vaccines Ltd, General Director of Pharmaq Vietnam,
the Food and Agriculture Organisation and Aquaculture Underwriting and
Insurance Management Services Ltd