Approaches For the New Generation Veterinary Vaccines
The field of veterinary vaccinology is advancing rapidly, driven by the need for more effective, safe, and versatile vaccines to address emerging challenges in animal health. The development of next-generation veterinary vaccines involves innovative approaches that harness cutting-edge technologies and scientific insights. This article explores several key strategies and technologies employed in the quest for more advanced veterinary vaccines.
The practice of vaccination for the prevention of animal disease has been used for centuries and has proven to be a powerful tool for the alleviation of animal suffering as well as the economic well being of producers of animal products. Most of the current veterinary vaccines are based on the use of either killed organisms or their products or live attenuated organisms. The development of these vaccines has not relied on knowledge of the immune responses that mediate immunity. Significant advances have been made primarily by the development of new culture techniques, improved attenuation procedures and better adjuvants. While there is some scope for further efforts to develop vaccines along these lines, there are many diseases for which the more empirical methods are unlikely to be successful. The approaches used in the development of vaccines have expanded rapidly as the result of increased knowledge of the mechanisms by which protective immunity is induced, and the explosion of genomic data on both pathogens and their hosts. The associated evolution of new technology in the field of molecular biology and immunology has furthermore had a large impact on the development of new vaccine strategies and the quality of the products that are produced.
The aim of any vaccination policy in any species is to challenge the individual with a “controlled” dose of an immunogenic organism (bacterium, virus, mycoplasma, fungus, etc) in order to stimulate an immune reaction that will prime the animal’s immune system to respond quickly and effectively to any future field challenge. Thus, vaccination is designed to prevent future disease. The advances in the knowledge about the immune response and molecular biology have allowed the identification of a large number of infectious agents and proteins of immunological interest and their expression in different vectors of amplification. The elimination of those proteins that are not of immunological interest or are not related to the virulence of the agent is now possible. Thus, new vaccines have been created which do not contain the whole infectious agent and allows the serological discrimination between sick and vaccinated animals. The basis of these new vaccines is, in the first place, the identification of the proteins of the infectious agent that are able to induce an immune response in a similar way to that produced by the whole agent. Secondly, the identification of those proteins that are not immunogenic, do not have a role in replication, or that are related to virulence. Using genetic engineering, the genes coded for these proteins can be selected, cloned and expressed using different vectors and they can also be eliminated by selective deletion. A variation of this system is the chemical production of the selected proteins once they have been identified. Another interesting aspect, when obtaining these new vaccines, is the possibility of incorporating the immunologically interesting proteins. These would be sequences of other antigens capable of increasing the stimulation of B and T lymphocytes, and even the release of cytokines.
Types of new generation vaccines
- Inactivated proteins based vaccines
a) Subunit Vaccines by Recombinant DNA technique.
This technique is based on the production of proteins from an infectious agent without using the microorganism. Once the relevant proteins from an etiologic agent has been identified and sequenced, using genetic engineering techniques the DNA fragment codifying these proteins is isolated and then inserted into a plasmid that acts as the vector for the transference. Later, this is inserted in the expression vector. Large quantities of a protein (subunit) are produced (sometimes more than one protein is produced) and it can be used as a subunit vaccine. The most frequently used vectors for expression are bacteria, especially E. coli, yeasts and baculovirus. Baculovirus are being increasingly used for the production of subunit vaccines due to their great capability of expression. Baculovirus is an insect virus able to replicate in established insect cell lines using this system, different proteins against several animal viruses have been produced in insect cells: blue tongue disease, porcine parvovirus, and African equine fever. In some cases, the production of several proteins at the same time simulating the virion particle (“Virus like particles” of VLP), has been possible. This is the case with blue-tongue disease; the obtained product has a high immunogenic capability.
b) Synthetic Vaccines by production of synthetic proteins
In synthetic vaccines epitopes or antigenic determinants are identified in the complex structure of a protein Example in Foot and mouth disease the epitope is VP-1 protein which is located between amino acids 140 and 160, it is then possible to chemically synthesize them and then produce a synthetic peptide identical to that of the virus this is known as a synthetic vaccine. However, the number of protected animals (in the case of foot-and- mouth disease) is less than 50% of the total disease.
Live deleted vaccines
The genomic structure of some microorganisms has been modified to make live deleted vaccines. In this vaccine the genes that codes for the virulence proteins have been eliminated and so attenuated strains that are safe and stable can be produced example Aujeszky´s disease virus vaccine.
III. Live Recombinant Vaccines
Live recombinant vaccines are based on the use of a live microorganism (virus or bacteria) that acts as a vector for the expression of genes from another organism. The new recombinant microorganism can be used as a vaccine for both organisms.
a) Bacterial vectors
In general bacterial vectors are attenuated by deletion of genes required for key metabolic processes or genes associated for virulence. Although they are not used routinely in animals, rapid progress is being made in developing and evaluating different bacteria as vectors. For several years, BCG (Bacillus Calmette–Guerin) and Salmonella have been developed as vectors for delivering vaccine antigens to animals and the latter has been used for the generation of live vaccine strains for poultry. There are currently a number of other bacterial vectors being developed based on commensal microorganisms (Lactococcus, Streptococcus,Lactobacillus and Staphylococcus) or attenuated pathogenic organisms (Shigella, Bacillus, Yersinia, Vibrio,Cornebacteria, and Bordetella), all of which are being evaluated for their ability to induce protective immunity.
b) Viral vectors
Most viral vectors are developed using viruses that are associated with mild or no disease or using viruses that are pathogenic but attenuated by deletion of virulence genes. Replication competent virus vectors, which can produce progeny virus, as well as replication-defective virus vectors, which do not produce progeny virus, have been developed and evaluated as vaccine delivery vehicles. A number of commercial vaccines based on DNA virus vectors, including poxviruses and herpesviruses, have been successfully licensed for use in veterinary medicine.
DNA Vaccines
The fraction of DNA containing the gene of the protein able to induce an effective immune response has been identified, purified and inserted in a plasmid that acts as a vector. Animal cells capture these plasmids and then incorporate them into the cell nucleus, allowing the expression of the foreign gene and the production of the protein. This protein is released to the extracellular space, where it is recognized by the immune system in its natural form, just as happens during a field infection and induces efficient immune response.
Reverse Genetics vaccine
The development of a reverse genetics system for a range of different RNA and DNA viruses has revolutionized the field of virology by making it possible to introduce designed mutations, insertions and deletions into the viral genome of live viruses. It has by now been used in a range of applications that include the attenuation of viruses,the modification of host specificity and the generation of replication-deficient viruses. These strategies have also been applied to the development of new vaccine strategies and are widely used in the characterisation of the structure and function of individual viral genes and coding sequences. The technology of reverse genetics involves the generation of a cloned copy of complementary DNA (cDNA) from RNA by reverse transcription in vitro, manipulating DNA in vitro followed by generating the modified live virus by transfection of permissive cells with the cloned DNA(s).
Chimeric viruses vaccine
Chimeric viruses are defined as recombinant viruses that may contain parts of two closely related viral genomes. For example, a chimeric virus could be one that contains structural genes of one viral serotype and nonstructural genes of another serotype of the same virus. lternatively, a chimeric virus would be one that contains part of the genome from different members elonging to the same virus family. In principle, chimeric viruses display the biological characteristics of both the parent viruses. One of the main advantages of this approach is that a single dose of chimeric virus delivers the complete repertoire of antigens closely resembling the pathogen(s), which can induce protective immune response against multiple viral pathogens belonging to or different serotypes of the same viral pathogen. New generation vaccines act upon the immune system in different ways depending on the type of vaccine. Subunit vaccines or vaccines based on synthetic proteins (inactivated proteins) act in a way similar to that of conventional inactivated vaccines, although usually more antigen is required to induce similar responses because they are less antigenic. The most important advantage of these vaccines is the lack of the entire infectious agent. This makes it possible to differentiate between vaccinated and sick animals. This characteristic is even more important in deleted live vaccines or recombinant vaccines, which being live vaccines, induce better immune responses than those of the inactivated proteins. DNA vaccines, consisting of a DNA fragment bound to a promoter, evoke both humoral and cell-mediated immunity. This type of vaccine seems very promising for future therapy. New generation vaccines solve some of the problems usually produced by the use of conventional vaccines 1. Discrimination between sick and vaccinated animals: This is one of the most important advantages of new generation vaccines compared to conventional vaccines. Example: In the case of Aujeszky´s disease, the use of gE-negative vaccines allows the implementation of eradication programs because the differentiation of sick from vaccinated animals is possible, vaccinated ones have only antibodies against gpII (not against gE) while carriers or sick animals have antibodies against both gE and gpII. 2. Cold chain: Sub-unit and synthetic vaccines do not require a cold chain as conventional vaccines. 3. Safety: Sub-unit or synthetic protein vaccines avoid the problem of incomplete inactivation that can be present in some of the inactivated conventional vaccines. These new generation vaccines do not need to be inactivated because they are made only of proteins. Deleted or recombinant vaccines also solve the problem of a potential reversion to the virulent form.
Subunit Vaccines:
Traditional vaccines often use weakened or inactivated pathogens. Subunit vaccines, on the other hand, focus on specific components of the pathogen, such as proteins or peptides. This approach enhances safety by avoiding the use of live organisms while allowing for targeted immune responses against critical antigens.
Recombinant DNA Technology:
Recombinant DNA technology enables the insertion of specific genes into the DNA of a host organism, typically bacteria or yeast, to produce desired antigens. This approach allows for the large-scale production of antigens, facilitating the development of vaccines against a wide range of pathogens.
Virus-Like Particle (VLP) Vaccines:
VLP vaccines mimic the structure of viruses without containing genetic material, making them non-infectious. This approach induces a robust immune response by presenting antigens in a manner that closely resembles natural infections, enhancing efficacy and safety.
Nanoparticle Vaccines:
Nanoparticle vaccines utilize nanoscale materials, often made of proteins or lipids, to deliver antigens. This approach enhances antigen stability, facilitates controlled release, and allows for the incorporation of multiple antigens, resulting in improved immune responses.
RNA and DNA Vaccines:
RNA and DNA vaccines represent a revolutionary approach where genetic material encoding antigens is directly introduced into the host cells. This stimulates the host to produce the antigens internally, mimicking a natural infection and eliciting a robust immune response.
Adjuvants and Immunomodulators:
The addition of adjuvants or immunomodulators to vaccines enhances their effectiveness by boosting the immune response. Modern veterinary vaccines often incorporate novel adjuvants to improve antigen presentation and stimulate a more robust and long-lasting immunity.
Reverse Vaccinology and Bioinformatics:
The integration of bioinformatics and genomics in vaccine development, known as reverse vaccinology, involves the systematic analysis of microbial genomes to identify potential vaccine candidates. This approach accelerates the discovery of novel antigens and aids in the rational design of vaccines.
Omics Technologies:
Advancements in omics technologies, including genomics, proteomics, and metabolomics, enable a comprehensive understanding of host-pathogen interactions. This information is invaluable for identifying suitable vaccine candidates and optimizing vaccine formulations.
Plant-Based Vaccines:
Plants can be engineered to produce antigens, offering a cost-effective and scalable platform for vaccine production. Plant-based vaccines present an innovative approach that can overcome traditional challenges associated with manufacturing and distribution.
Synthetic Biology:
Synthetic biology involves the design and construction of new biological entities for specific purposes. In the context of veterinary vaccines, synthetic biology allows for the creation of designer antigens or immune stimulants with tailored properties for optimal vaccine efficacy.
Conclusion
The development of next-generation veterinary vaccines relies on a diverse array of innovative approaches and technologies. From subunit vaccines and recombinant DNA technology to RNA and DNA vaccines, the landscape of veterinary vaccinology is evolving rapidly. These approaches not only enhance the safety and efficacy of vaccines but also enable the rapid response to emerging infectious diseases. As the field continues to advance, the integration of cutting-edge technologies and interdisciplinary collaboration will play a pivotal role in shaping the future of veterinary vaccine development, ultimately contributing to improved animal health and global food security.
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.
