Recombinant and Synthetic Vaccines Overview

Recombinant and Synthetic Vaccines

• Infectious diseases cause 30% to 50% of deaths in developing countries.
• Effective chemotherapeutic agents are often unavailable or too expensive.
• Vaccines are crucial in combating infectious diseases in developing nations.
• Developed countries experience a lower rate of infectious disease mortality (4%-8%).

Widespread Use of Vaccination

• Smallpox vaccination
• Diphtheria (caused by Corynebacterium diphtheriae)
• Poliomyelitis vaccination

Cost-Efficiency

• Vaccination is less expensive than treating existing illnesses.
• Vaccines remain vital in veterinary medicine.
• Farm animals in close proximity increase cross-infection rates.

Recombinant and Synthetic Vaccines - Table 5.1

• Attenuated live pathogens: Measles, Mumps, Rubella (German measles), Varicella (chickenpox) use attenuated live viruses.
• Inactivated whole pathogens: Poliomyelitis uses inactivated viruses.
• Modified components of pathogens: Diphtheria and Tetanus use toxoids, Pertussis uses components of the pathogen.
• Recombinant DNA derived subunit vaccine: Hepatitis B uses surface antigens produced in yeast cells.

Recombinant and Synthetic Vaccines - Chronology

• Smallpox, 1800
• Rabies, 1900
• Mention of additional diseases: Hepatitis B, Pneumococcus, Meningococcus, Rubella, Mumps, Measles, Polio (Sabin and Salk), Yellow fever, Influenza, Pertussis, Cholera, Tetanus, Tuberculosis, Diphtheria, and Typhoid.

Problems with Traditional Vaccines

• Traditional vaccines are live or killed.
• Live vaccines contain weakened viral or bacterial strains; prolonged storage or suboptimal conditions.
• Killed vaccines contain killed whole cells or inactivated toxin proteins (toxoids).
• Many traditional vaccines are effective but new vaccines and techniques are often necessary.
• Vaccines for various diseases are not yet developed, or those developed are not sufficiently effective or safe.

Problems with Traditional Vaccines - (Table 5.2)

• Shows examples of diseases with no/limited effective vaccines: AIDS, Diarrhea, Tuberculosis, Malaria, Hepatitis C, Leishmaniasis, Trypanosomiasis, Schistosomiasis, and Chagas disease.
• Mentions data sources.

Problems with Traditional Vaccines - Graph

• Shows the incidence of poliomyelitis cases and vaccine-associated paralytic poliomyelitis (VAPP) in the United States from 1960 to 1996.

Problems with Traditional Vaccines - Continued

• Danger of reversion to virulent state.
• Need for tissue culture cell growth – possible hidden viruses.
• Potential for adverse reactions from vaccines themselves.
• "Whole-cell" vaccine for pertussis may cause adverse effects.
• Potential risks to workers involved in vaccine production.
• Potential issues with complete killing/inactivation rates.
• Difficulty with sufficient vaccine quantities.

Impact of Biotechnology on Vaccine Development

• Biotechnology advancements lead to new vaccine types.
• Targeting specific new pathogen targets.
• Improved vaccine efficacy/safety.
• Protective antigens—molecules generating immunity.
• Use of recombinant DNA methods for vaccine production.
• Utilizing non-pathogenic organisms.

Impact of Biotechnology on Vaccine Development - Continued

• Recombinant DNA enables vaccine production even when pathogens are hard/impossible to cultivate.
• New vaccines often target one/few molecules.
• Subunit vaccines: new vaccines contain one or some of the original pathogen molecules.
• Acellular pertussis vaccine, conjugate polysaccharide vaccines - developed using non-recombinant DNA methods.
• Hepatitis B subunit vaccine using recombinant DNA techniques.

Acellular Pertussis Vaccine

• Pertussis/whooping cough is a significant childhood disease.
• Before vaccines, it resulted in illness and high death rates in the US.
• WHO reports significantly higher rates globally.
• Traditional whole-cell vaccine reduced cases but caused significant safety concerns (infant death, decreased efficacy), leading to the development of acellular vaccines.
• Acellular vaccines use purified pertussis toxin (inactivated), and other components.
• Acellular vaccines are generally more effective and safe than the older whole cell vaccine.
• Chiron now produces a recombinant DNA-derived pertussis toxin vaccine in Europe. The toxic activity is inactivated without altering the protein structure.

Conjugate Polysaccharide Vaccines

• Effective vaccines for invasive Haemophilus influenzae type b(Hib) and Streptococcus pneumoniae cases.
• Protective antigen in these vaccines is the polysaccharide capsule.
• Polysaccharides provide immunity in adults, but not necessarily infants.
• Conjugation to a carrier protein is necessary to generate adequate immunity in infants.

Conjugate H. Influenzae Vaccines

• First licensed conjugate Hib vaccines in 1990.
• Pneumococcal conjugate vaccines in 2000.
• Improved versions reduce cases and are crucial in reducing disease.

Other Information

• Mention of CRM197, a diphtheria toxin variant, used in some conjugate vaccines.

This quiz covers the critical role of recombinant and synthetic vaccines in combating infectious diseases, particularly in developing nations. It discusses the cost-efficiency of vaccination and highlights key vaccinations such as those for smallpox and poliomyelitis. Understand how different types of vaccines, including attenuated and inactivated pathogens, play a significant role in both human and veterinary medicine.