Recent Development of Vaccination in Fish

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Recent Development of Vaccination in Fish

Aquaculture, as a critical component of the global food industry, faces numerous challenges, including infectious diseases that can significantly impact fish health and production. Vaccination has emerged as a key strategy to mitigate the impact of these diseases in aquaculture. Recent developments in fish vaccination have seen the application of innovative technologies and approaches to enhance efficacy, safety, and sustainability. This article explores some of the notable advancements in fish vaccination and their implications for the aquaculture industry.

Aquaculture has been globally recognized as the fastest growing food production sector (FAO). The intensive farming of finfishes and shellfishes has led to an imbalance of best culture conditions that shows enhanced susceptibility to infectious disease. Increased incidence of microbial diseases in aquaculture system is the major obstacle within the success of the business. Use of antibiotics has attracted lot of criticism as a result of the problems like antibiotic residues, bacterial drug resistance and toxicity. In this present scenario, vaccination would be the best alternative to combat bacterial and viral disease for thesustainable aquaculture. The primary report on fish vaccination was by David C. B. Duff and he is regarded as “Father of fish vaccination”. It is standard that the appearance and development of a fish disease process is the result of theinteraction between infectious agent, host, and environment. Therefore, only multidisciplinary studies involving knowledge of the characteristics of the potential pathogenic microorganisms for fish, aspects of the biology of the fish hosts, moreover as a better understanding of the environmental factors affecting them, can enable the appliance of adequate measures to stop and management the most diseases limiting the production of freshwater and marine fishes. Regarding the infectious fish diseases caused by microorganism, though pathogenic species are described within the majority of the present taxonomical groups, only a comparatively small variety are responsiblefor necessary economic losses in the extensive cultures worldwide. Vaccination is becoming a more and more vital a part of aquaculture, since it is considered a cost effective method ofcontrolling different threatening diseases. The term vaccination strategy has been defined to include the decision as to which diseases to vaccinate against, as well as the vaccine type, vaccination method, the timing of vaccination and the use of revaccination. Aquaculture still faces serious economic impacts as a result of the loss of animals to disease. A conservative estimate of 5% losses as a result of disease means that the finfish aquaculture business loses over $1 billion annually on a global scale. One proven way to prevent expensive disease outbreaks is to immunize fish against common or identified pathogens. Current vaccination schemes still result in losses, however, and this might be due in part to immunizing agent design. Vaccinesare presently designed using state of the art knowledge of immune responses that is predicated totally on mammalian studies. One necessary thought for development and exploitation of vaccines includes the applying strategies and procedures that can be integrated into the normal production protocols of the target fish species that are relevant to the standard ecology and epidemiology of the disease (i.e. seasonal incidence, fish size, host and geographic range of the disease).

CONCEPT OF VACCINATION

Vaccination could be a most effective technique of protective fish from diseases. Vaccination could be a method by that a protective immunologic response is start in an animal by administration of vaccines. Vaccines are preparations of antigens derived from infective organisms, rendered non-pathogenic by various means, which can stimulate immune system of the animal to extend the resistance to the disease on natural encountered with pathogens. Once stimulated by a vaccine, the antibodyproducing cells, known as B lymphocytes, stay supersensitive and prepared to respond to the agent should it ever gain entry to the body.

IMPORTANCE OF VACCINATION

· Vaccines are not a similar as antibiotics and usually won\’t be effective for stopping a disease outbreak once it’s begun. · Vaccines are used to stop a specific disease outbreak from occurring and are not a therapy. · Its efficiency exists for a longer duration with one or more treatments. · No cyanogenetic side effects and healthy fish have higher growth performance. · No accumulation of toxic residues· Pathogen won’t develop resistance. · Theoretically it can management any microorganism and viral disease. · No environmental impact.

PROPERTIES OF THE IDEAL VACCINE

· Is safe for the fish, the person(s) vaccinating the fish, and therefore the consumer; · Protects against a broad strain or microorganism sort and provides 100% protection; · Provides long-lived protection, a minimum of as long as the production cycle; · Is simply applied; · Is effective during a variety of fish species; · Is cost effective; and· Is readily licensed and registered (Grisez and tan 2005).

TYPES OF VACCINES

The optimum way of development of an effective vaccine entails the identification of the key virulence factors. Further, the induction of the reaction should be optimized in order that the vaccinated animal develops a protecting immunity against the pathogen. So far, most vaccines employed in aquaculture are developed through associate empirical process, themain points of which are able to be which will within the ensuing paragraphs.

Inactivated Vaccines

 Bacterins with antigens of Gram-negative organisms such as Vibrio anguillarum, Vibrio ordalii, Vibrio salmonicida and Yersinia ruckerii have been produced by broth fermentation and subsequent formalin inactivation. Administration is by injection or immersion. Provided that the serotypes used for vaccine preparation cover the field strains and that the vaccines are used correctly, these vaccines are effective and give negligible side effects (Stevenson, 1997; Toranzo et al., 1997). For some diseases, including infections with Aeromonas salmonicida subsp. salmonicida, an acceptable level of protection can only be achieved by immunisation withadjuvanted bacterins that are delivered by injection (Ellis, 1997; Midtlyng, 1997). Most vaccines used in aquaculture to date have been inactivated, bacterial vaccines. However, during recent years, inactivated virus vaccines against infectious pancreatic necrosis (IPN) in Atlantic salmon and grass carp haemorrhage disease have been used with some success (Dixon, 1997).

Live Vaccines

Live, attenuated vaccines should potentially have many advantages in aquaculture(Benmansour and de Kinkelin, 1997). Vaccination with a live vaccine is in reality an infection (with an attenuated strain), and if the vaccine strain is shed by vaccinated fish, an effective dissemination of the antigen in the population would take place over an extended time period. Live vaccines also have the advantage that they stimulate the cellular branch of the immune system (Marsden et al., 1996). Finally, attenuated vaccines have some economic advantages in terms of simple delivery and low dose requirements due to multiplication in the fish. Some of the live vaccines tested experimentally elicitprotective immunity, which is comparable with that of inactivated vaccines against the same microorganism (Marsden et al., 1998). However, live vaccines for fish are used under natural conditions and consequently, the requirements for documentation of the risks of reversion to virulence and uncontrolled environmental spreading should be emphasized. Although scientific risk assessments of using live vaccines have not been presented, there seems to be a general view that the risks associated with live vaccines in aquaculture, whether produced by conventional methods or by recombinant techniques, should be scrutinized. Live, attenuated vaccines haveso far only been allowed for field trial purposes in the catfish industry in the US.

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Vaccines based on DNA

In recent years, various vectors have been used for cost-effective production of sufficient quantities of protective antigens by recombinant DNA technology. In aquaculture, research on recombinant vaccines has focused on viral vaccines. Glycoproteins of the viruses causing viral hemorrhagic septicemia (VHS) and infectious hematopoietic necrosis (IHN) in rainbow trout elicit production of moderate levels of protective, neutralizing antibodies under experimental conditions (Lorenzen et al., 1993). These glycoproteins have been expressed in Escherichia coli, and more recently in attenuated strains of A. salmonicida (Noonan et al., 1995). So far, the only licensed recombinant fish vaccine is for protection against IPN (Frost and Ness, 1997). The VP2 sequence is expressed in E. coli producing an rVP2 peptide that induces production of a-IPNV specific antibodies (Christie, 1997). The adjuvanted recombinant vaccine is given by injection to pre-smolts. Genetic immunisation using naked DNA is the most recent approach in vaccine design (Babiuk et al., 1996). This technology is based on the observationsthat skeletal muscle cell injected with purified plasmid DNA express plasmidencoded proteins. In mammals, experimental DNA vaccines have been used successfully in immunisation experiments with several important viruses including influenza virus and rabies virus. In fish, injection of plasmid DNA containing genes encoding glycoproteins or nucleocapsid protein, protected against challenge by IHN (Anderson et al., 1996) and VHS (Lorenzen et al., 1998). DNA vaccines have advantages over conventional vaccines. In mammals, the specific immune response after DNA vaccination encompasses antibodies, Thelper cells, as well as cytotoxic cells. However, before DNA vaccines are applied in commercial enterprises in aquaculture, safety for fish, environment and the consumer have to be addressed. As the DNA-sequence encodes only a single viral gene, there should be no possibility of reversion to virulence, which is a critical factor in relation to environmental safety in aquaculture.

 Biofilm vaccines

Bacterial biofilm is a colony of high density of cell embedded in a glycocalyx matrix on a substrate, which has been demonstrated to be resistant to action of antibiotics chemicals and host immune system. Bacteria biofilm on suitable substrate after inactivation can be used as a successful oral vaccine.

 Recombinant protein vaccines

It starts with identification of immunogenic subunit or protein from a pathogen of interest followed by the genes involved in coding for them which can be introduced into a vector, over expressed in expression hosts and can be used as recombinant protein vaccines.

VACCINES AGAINST SOME FISH DISEASES

(i) Bacterial vaccines Antigens from V. anguillarum, V. ordalii and V. salmonicida have been used for a long time in fish vaccines (Toranzo et al., 1997). These microorganisms cause diseases that in their classical form are a septicaemia. V. vulnificus and V. viscosus present new challenges for the fish vaccinologists, the former being an opportunistic human pathogen and the latter causing `winter ulcer’ in Atlantic salmon, which severely affect the commercial value of the fish. An inactivated vaccine against V. viscosus has been shown to give protection(Vinitnantharat et al., 1999). So far, no commercial vaccine containing V. vulnificus antigens is available, but a toxoided bacterin with Spanish and Japanese strains has been shown to be protective both inlaboratory experiments and in commercial farms (Toranzo et al., 1997). The successful use of immunoprophylaxis to prevent furunculosis caused by A. salmonicida subsp. salmonicida in salmonid fish suggests that diseases caused by atypical A. salmonicida can also be controlled by vaccination. Atypical A. salmonicida has been isolated from salmonids and nonsalmonids in fresh water as well as in marine environments all over the world (Wiklund and Dalsgaard, 1998). So far, successful vaccination has been reported from Iceland where injectable, adjuvanted vaccines based on A. salmonicida subsp. achromogenes were found to induce theproduction of antibodies and provide protection against atypical furunculosis in salmon (Gudmundsdottir et al., 1997). Extracellular enzymes, capsular polysaccharides, LPS and iron regulated outer membrane proteins are among the factors proposed to be important for the virulence of Pasteurella piscicida (Romalde and Magarinos, 1997). Vaccines covering some of these virulence determinants are now being introduced in several Mediterranean countries (Gravningen et al., 1998). The severe losses due to enteric septicaemia of channel catfish caused by Edwardsiella ictaluri have generatedcommunity, but so far with no solution for the affected industry. Neither immersion nor oral preparations with inactivated antigens provided protection against infection with this facultative intracellular pathogen (Shoemaker and Klesius, 1997; Thune et al., 1997). An injectable vaccine gave a low, but significant protection (Thune et al., 1997), whereas a preparation with live attenuated microorganisms was found to stimulate antibody production, macrophage-mediated killing, as well as protection in challenge experiments (Shoemaker and Klesius, 1997). Among diseases caused by Gram-positive bacteria, enterococcosis (streptococcosis) is the best candidate for successful vaccine development. This group of diseases iscaused by several species of microorganisms which recently have been reclassified taxonomically using molecular tools (Bercovier et al., 1997). Preparations with inactivated bacteria given intraperitoneally were found to stimulate protective immunity in turbot, rainbow trout and tilapia (Toranzo et al., 1995; Akhlaghi et al., 1996; Bercovier et al., 1997).

 (ii) Viral vaccines

Antigens produced by several viruses administered by injection or immersionhave been shown to elicit protective immunity. However, for several viral diseases including VHS, IHN, spring viraemia of carp and channel catfish virus disease, the level of protection has been too low for commercial use (Dixon, 1997; Lorenzen and Olesen, 1997; Winton, 1997). Vaccines against IPN with antigens from inactivated virus or produced by recombinant technology, respectively, are in common use in Norway (Frost and Ness, 1997). Administration of adjuvanted preparations by injection is a prerequisite. However, protection is not welldocumented. Vaccination against grass carp haemorrhage disease with live or inactivated vaccines reduces mortality significantly. An inactivated, nonadjuvanted vaccine for parenteral administration is produced commercially in China (Dixon, 1997). Red sea bream iridoviral disease is a threatening condition for Japanese marine aquaculture. Red sea bream immunised with inactivated iridoviral antigens were significantly better protected than non-vaccinated fish after experimental infection (Nakajima et al., 1997).

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(iii) Parasitic vaccines

There are not any commercial vaccines against parasitic diseases in fish. However, throughout recent years studies on the mechanisms of response to totally different parasites are performed (Secombes and Chappell, 1996; Woo, 1996). One amongst the candidate diseases for immunoprophylaxis is cryptobiosis. In rainbow trout vaccinated with a live Cryptobia salmositica vaccine, complement fixing antibodies were demonstrated and also the vaccinated fish showed protection once challenged with the infectivehaemoflagellate (Li and Woo, 1997). The great challenge is to regulate salmon louse (Lepeophtheirus salmonis) infection by vaccination. The success with vaccination against Boophilus tick infections in cattle provides hope for a similar strategy against ectoparasites of fish. tries are created to identify enzymes of importance for digestion of put in sea lice internal organ, however vaccination studies supported these antigen preparations have so far not proven successful (Roper et al., 1995).

List of fish vaccines developed

VACCINES                          SPECIES                             DISEASE

Aeromonas salmonicida Bacterin —-Atlantic salmon —Furunculosis

Vibrio anguillarum-Ordalii-Yersinia ruckeri Bacterin Rainbow trout Vibriosis,

yersiniosis (enteric red- mouth disease) Yersinia ruckeri Bacterin Salmonids Yersiniosis (enteric red-mouth disease)

Vibrio salmonicida Bacterin Salmonids Vibriosis

Vibrio anguillarum-salmonicida Bacterin Salmonids Vibriosis

Aeromonas salmonicida Bacterin Salmonids Furunculosis

Edwardsiella ictaluri Bacterin Catfish Enteric septicaemia

Spring viraemia of carp virus Common carp Spring viraemia of Carp

Koi herpes virus (KHV) Koi carp Koi herpes virus (KHV) disease

Biofilm and free-cell vaccines of Aeromonas hydrophila Indian major carps Dropsy

Streptococcus agalactiae (group B) vaccine Tilapia  Streptococcosis

Betanodavirus Grouper  Betanodavirus disease

METHODS OF VACCINE ADMINISTRATION

Vaccines are administered to fish in one among 3 ways: by immersion, by mouth, or by injection. Every methods has its benefits and drawbacks. The foremost effective method can depend on the pathogen and its natural route of infection, the life stage of the fish, production techniques, and alternative supply concerns. A specific route of administration or even multiple applications using totally differentstrategies is also necessary for adequate protection. 1) Immersion method The biomass of the fish to be vaccinated is calculated since the vaccine is administered on a combined body-weight basis. Additionally the minimum size of the fish is checked since there will be a minimum size below that fish shouldn’t be vaccinated – the vaccine data sheet and package insert will provide info on the minimum size of fish for vaccination with the actual vaccine. The vaccine is diluted according to specific directions using some of the water during which the fish are kept, and the fish are immersed in batches within the diluted vaccine for the recommended time usually around thirty seconds. Every bottle of targeted vaccine are adequate to vaccinate a designated weight of fish. Throughout immersion care should be taken to aerate the diluted vaccine while the fish are in it. Also follow the vaccine instructions in respect of minimum temperatures below that fish shouldn’t be vaccinated. this is often as a result of the fish immune reaction can depend upon the temperature of the water in which the fish are kept, and below temperatures like 4 – 5ºC the response will be insufficient to confirm adequate protection. All fish vaccines can carry the recommendation that only healthy fish should be vaccinated. Also individual vaccines shouldn’t be mixed.

Oral method

The method of oral administration can vary according to the vaccine. The three methods are top-dressing the finished feed with the vaccine powder using an adhesive agent such as edible oil or may be gelatin, spraydressing the finished feed if the vaccine is in liquid form, or incorporating the vaccine into the feed throughout the feed production process. The biomass of the fish to be vaccinated should be estimated and the vaccine mixed with the feed according to the manufacturer’s instructions. With liquid vaccines, bring the vaccine to room temperature (20oC) for 1 hour before use to allow the vaccine to become more liquid. If any separation occurs, shake the bottle vigorously until the separated layers are completely distributed. Turn the required weight of feed pellets in a mixer, e.g. a concrete mixer, and slowly pour or spray the vaccine directly onto the pellets. If a sprayer is used, it should be set to deliver a coarse spray without risk of aerosol particlegeneration and the spray container must be completely emptied during the mixing operation. Mix the pellets for at least 2 minutes after all the vaccine has been added. Keep the prepared feed for 1 hour before feeding, to permit the vaccine to impregnate the pellets completely. The vaccine-incorporated feed should then be fed according to the vaccine manufacturer’s instructions, as a course of vaccine may be required to induce an adequate immune response. The vaccine manufacturer’s guidance on storage of feed containing vaccine should be observed, as well as the minimum size of fish which can be vaccinated with any particular vaccine.

Injection method

The vaccine-incorporated feed should then be fed according to the vaccine manufacturer’s instructions, as a course of vaccine may be required to induce an adequate immune response. The vaccine manufacturer’s guidance on storage of feed containing vaccine should be observed, as well as the minimum size of fish which can be vaccinated with any particular vaccine.

RECENT DEVELOPMENT IN FISH VACCINOLOGY

During the last twenty years vaccination has become established as a very important technique for prevention of infectious diseases in farmed fish, mainly salmonid species. So far, most commercial vaccines are inactivated vaccines administered by injection or immersion. Microorganism infections caused by gram-negative microorganism like vibrio sp., Aeromonas sp., and Yersinia sp. are effectively controlled by vaccination. With furunculosis, the success is attributed to the utilization of injectable vaccines containing adjuvants. Vaccines against virus infections, as well as infectious pancreatic necrosis, have also been utilized in commercial fish farming. Vaccines against many alternative microorganism and viral infections are studied and located to be technically possible. The positive effect of vaccination in farmed fish is reduced mortality. However, for the longer term of the fish farming industry it\’s additionally necessary that vaccination contributes to a sustainable biological production with negligible consumption of antibiotics.

THE GENERAL KEY RULES OF FISH VACCINATION

Do not let vaccines solve your farming problems. Events or practices like overstocking, undue stress, or poor water quality will cause breakdowns in vaccine protection. · Only vaccinate healthy fish. The performance of vaccines is incredibly dependent on the health status of the fish at the time of vaccination. Vaccines can not be expected to provide sensible or long term protection if the fish are sick, in poor condition, or they are carriers of pathogens once vaccinated. · Allow adequate time for immunity to develop. Immunity takes time to develop and therefore vaccinated fish are not directly protected. Thus, vaccinated fish should be maintained throughout this point within the less stressful conditions as possible. The time of the event of immunity depends mainly upon the surrounding water temperature (i.e. at 10ºC it takes 15-20 days). · Strictly follow the recommendations of vaccine usage once immunizing fish. don\’t attempt to shorten the recommended time of exposure to the vaccines; don’t modify the dilution or dose recommended; don’t overload the net once fish are vaccinated by dip immersion; do make sure that the water used to dilute the vaccine could be a similar temperature to it during which the fish are being held; don’t use the vaccine when the expiry knowledge. · Do not expect vaccines to eradicate disease. If vaccines against a specific disease are used routinely on the farm, proof of this disease can mostly disappear. However, this doesn’t mean that the organism that causes the disease has been eradicated. In fact, it’s still present and capable of infecting vulnerable unvaccinated fish.

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FUTURE PROSPECTS ·

To achieve progress in fish vaccinology, a rise within the co-operation between basic and technology (i.e., between the immunologist/microbiologist and also the vaccinologist) is required. · Since there is not continuously correlation between the main antigens expressed in vitro and those expressed in vivo, the event of simpler vaccines for the diseases in aquaculture should rely in the identification of the vital immunogens expressed by the pathogens in vivo, and also the choice of in vitro conditions that maximize their expression. · Improvement in oral immunization with perishable micro particle-based vaccines to be used for booster vaccination. · Development of recent non-mineral oil adjuvants lacking aspect effects. · Development of polyvalent vaccines and standardization of a vaccination calendar applicable for every economically necessary fish species. · Investigation of the mechanisms of immunoglobulin transfer from prespawning females to offspring as a helpful method of protective fish against pathogens that have an effect on early life stages.

DNA Vaccines

Recent years have witnessed increased interest in DNA vaccines for fish. These vaccines involve the introduction of plasmid DNA containing specific pathogen-related genes into fish cells. DNA vaccines offer advantages such as rapid development, broad-spectrum protection, and the ability to differentiate infected from vaccinated animals (DIVA). Researchers are exploring the potential of DNA vaccines against various fish pathogens, including viruses and bacteria.

Viral Vector Vaccines

The use of viral vectors to deliver vaccine antigens has gained traction in fish vaccination. Viral vector vaccines utilize harmless viruses to carry and deliver antigens, eliciting a robust immune response. This approach allows for the development of multivalent vaccines, targeting multiple pathogens simultaneously. Viral vector vaccines show promise in providing long-lasting immunity and overcoming some of the challenges associated with traditional vaccines.

Nanoparticle-Based Vaccines

Nanoparticle-based vaccines represent an innovative approach in fish vaccination. Nanoparticles, often composed of lipids or proteins, serve as carriers for vaccine antigens. These carriers enhance antigen stability, facilitate controlled release, and improve the uptake of antigens by fish cells. Nanoparticle-based vaccines show potential for enhancing the immune response and providing protection against a variety of fish pathogens.

Oral Vaccination

Advancements in oral vaccination techniques offer a non-invasive and practical approach for fish immunization. Oral vaccines can be delivered through feed, making the vaccination process more cost-effective and scalable. Researchers are exploring various formulations, including encapsulated vaccines and antigen-coated feed, to enhance the efficacy of oral vaccination in fish.

Immune-Stimulating Adjuvants

The development of novel adjuvants plays a crucial role in enhancing the effectiveness of fish vaccines. Adjuvants stimulate the immune system, improving the recognition and response to vaccine antigens. Recent developments focus on identifying safe and effective adjuvants that enhance the innate and adaptive immune responses in fish, leading to improved vaccine efficacy.

Nanotechnology and Smart Delivery Systems

Nanotechnology has introduced smart delivery systems for fish vaccines, allowing for controlled and targeted antigen release. These systems can improve vaccine stability, reduce the frequency of booster vaccinations, and enhance the overall performance of fish vaccines. The use of nanotechnology in vaccine development aligns with the principles of precision aquaculture and sustainable disease management.

Future Perspectives

As the aquaculture industry continues to expand, the development of advanced vaccination strategies becomes increasingly critical. Future advancements in fish vaccination may involve the integration of genomics, transcriptomics, and immunomics to tailor vaccines for specific fish species and pathogens. Additionally, the exploration of immune-modulating compounds and the optimization of vaccination strategies for diverse aquaculture settings will contribute to the sustainability and resilience of the global fish farming industry.

Conclusion

Recent developments in fish vaccination underscore the commitment of researchers and industry stakeholders to address the challenges posed by infectious diseases in aquaculture. The integration of DNA vaccines, viral vectors, nanoparticles, oral vaccination, and advanced adjuvants reflects a multidimensional approach aimed at improving the efficacy and sustainability of fish vaccination programs. As these innovations continue to evolve, the aquaculture industry is poised to benefit from enhanced disease control, improved fish welfare, and increased productivity, contributing to the global supply of high-quality and sustainable seafood.In addition to optimizing farming and general management practices, use of vaccines continues to be limited, is turning into additional widespread in certain sectors of aquaculture for disease prevention. Varieties of vaccines are in use by the salmonid industry for many years. However, commercial vaccine development for aquaculture cultivation sectors, as well as producers of warm water fish, remains quite restricted. Larger demand by producers and increased levels of research and interest by manufacturers is helping to form vaccination an additional viable choice. Currently, vaccines are available for a few economically necessary microorganism and viral diseases. Vaccines for defense against parasitic and fungal diseases have not yet been developed. Vaccination should be considered a part of a comprehensive fish health management scheme, and not the only solution for a disease problem.

Compiled  & Shared by- This paper is a compilation of groupwork provided by the

Team, LITD (Livestock Institute of Training & Development)

 Image-Courtesy-Google

 Reference-On Request.

                      FISH VACCINE

CLINICAL POINTERS FOR PRACTICING VETS

                    FISH VACCINE

 

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