Fish Diseases and Management

7.4.1 Advanced vaccine development strategies

Molecular biology procedures have and will continue to have major impact on the preparation of veterinary/aquaculture vaccines. Products of recombinant technology may be easier to monitor because they may have specific markers introduced into or deleted from the vaccine.

Even though genetic information is often manipulated in live recombinant vaccines, there are significant safety concerns surrounding their usage. In general, safety and potency requirements should be consistent with those for other live vaccines. A potential always exists for adverse reactions to the vector agent being used, although this potential can be diminished by the inactivation or deletion of virulence factor genes in the vector virus. Other risks include adverse recombination events with wild-type infectious agents, changes in cell tropism or virulence due to genomic alterations, and potential undesired ecological effects. The latter can be of particular concern when spread occurs to a species in which the vector agent may differ in degree of attenuation.

Gene-deleted  vaccines
Virus genes coding for virulence can be deleted, leaving a virion that can be used in live virus vaccines with reduced virulence. Engineering a mutation of the thymidine kinase (TK) gene so that the vaccine has no detectable TK activity can generate a vaccine strain. In addition to a TK deletion, a second deletion removes a gene coding for viral glycoprotein that prevents antibodies being produced against the glycoprotein. This second deletion allows vaccinated animals to be identified by ELISA from naturally infected ones. Other constructs may have deletions in global genes and these deletion mutants are frequently unable to replicate without the addition of specifically required nutrients. The vaccine agent undergoes restricted replication in the vaccinate but is unable to continue replication cycles. This results in a vaccine that is capable of inducing an immune response in a similar way to other live vaccines, but which has greater safety because it will not persist in the animal or in the environment.