Molecular Biotechnology: Principles and Applications - Glick B., Pasternak J. 2002

Molecular Biotechnology of Microbial Systems
Vaccines

Vaccination promotes The Development of Immunity to pathogenic Microorganisms in the recipient, thereby protecting them from infection. In response to oral or parenteral administration of a vaccine, the host Organism produces Antibodies against the pathogen. Upon subsequent exposure, these antibodies lead to its inactivation (neutralization or destruction), block its proliferation, and prevent the Development of the disease.

The Effect of vaccination was discovered more than 200 years ago—in 1796—by the physician Edward Jenner. He experimentally proved that a person who had contracted cowpox, a relatively mild disease of cattle, became immune to smallpox. Smallpox was a highly contagious disease with a high mortality rate; even if the patient survived, they often suffered from various disfigurements, mental disorders, and blindness. Jenner publicly inoculated an 8-year-old boy, James Phipps, with cowpox, using exudate from a pustule of a person infected with cowpox, and then, after a certain period, twice inoculated the child with pus from a pustule of a smallpox patient. All manifestations of the disease were limited to redness at the vaccination site, which disappeared after a few days.

Previously, infectious diseases such as tuberculosis, smallpox, cholera, typhoid fever, bubonic plague, and polio were a real scourge for humanity. With the advent of Vaccines and Antibiotics, and the Structure/175.html">Implementation of preventive measures, these epidemic diseases were brought under control. However, protective measures eventually became ineffective, and new outbreaks occurred. In 1991, a cholera epidemic struck Peru; over the next three years, approximately 1 million cases were identified, and several thousand people died. Unfortunately, no vaccines exist for many Human and Animal diseases. Today, more than 2 billion people worldwide suffer from diseases that could be prevented by vaccination. Vaccines may also prove useful in preventing constantly emerging "new" diseases (such as AIDS).

As a rule, modern vaccines are based on killed (inactivated) pathogenic microorganisms or live, but non-virulent (attenuated) strains. To achieve this, a wild-type strain is grown in culture, purified, and then inactivated or modified so that it triggers an Immune Response effective enough against the virulent strain. Despite significant success in developing vaccines against diseases such as rubella, diphtheria, pertussis, tetanus, smallpox, and polio, The production of modern vaccines faces A number of limitations.

✵ Not all pathogenic microorganisms can be cultured, which is why vaccines have not been developed for many diseases.

✵ Obtaining animal and human Viruses requires expensive Animal Cell Cultures.

✵ The titer of animal and human viruses in culture and their rate of Replication are often very low, which increases vaccine production costs.

✵ Strict safety precautions must be observed to prevent laboratory personnel from becoming infected.

✵ If the manufacturing process is compromised, live or insufficiently attenuated virulent microorganisms may contaminate some vaccine batches, potentially leading to the unintentional spread of infection.

✵ Attenuated strains can revert to the original strain, making it necessary to constantly monitor virulence.

✵ Some diseases (e.g., AIDS) cannot be prevented using traditional vaccines.

✵ Most modern vaccines have a limited shelf life and remain active only at low temperatures, which complicates their use in developing countries.

Over the past decade, with the advancement of Recombinant DNA technology, it has become possible to create a new generation of vaccines that lack the disadvantages of traditional vaccines. Introduction/32.html">Genetic Engineering techniques are used for their development.

✵ The pathogenic microorganism is modified by deleting the genes responsible for virulence, while its ability to elicit an immune response is preserved. Such an organism can be safely used as a live vaccine, since growth in pure culture rules out the possibility of spontaneous restoration of the complete Gene.

✵ Live, non-pathogenic delivery systems are created to carry individual antigenic determinants of an unrelated pathogen. Such a delivery system promotes the development of a strong immune response against the pathogenic microorganism.

✵ If pathogenic microorganisms do not grow in culture, the genes encoding Proteins that contain the major antigenic determinants can be isolated, cloned, and expressed in an alternative host (e.g., E. coli or a mammalian cell line), and these Proteins can be used as "subunit" vaccines (see next section).

✵ Some pathogens act indirectly by triggering an autoimmune reaction against infected host Cells. For such diseases, a system for the specific destruction of target cells can be created by designing a gene that encodes a chimeric protein, one part of which binds to the infected cell while the other destroys it. Although this system is not a true vaccine, it acts only on infected cells, eliminating the very cause of the autoimmune reaction.

Since regulatory requirements for animal vaccines are less stringent, the first vaccines produced using recombinant DNA technology were those against FOOT-and-Mouth disease, rabies, dysentery, and piglet diarrhea. Other animal vaccines are being developed, and recombinant vaccines designed for humans are expected to appear soon (Table 11.1).