Lecture 8 Recombinant and Synthetic Vaccines PDF

Lecture 8: Recombinant and synthetic vaccines  RECOMBINANT AND SYNTHETIC VACCINES In developing countries, infectious diseases still cause 30% to 50% of all deaths Effective chemotherapeutic agents simply do not exist Too costly for much of the population to afford D...

Lecture 8: Recombinant and synthetic vaccines  RECOMBINANT AND SYNTHETIC VACCINES In developing countries, infectious diseases still cause 30% to 50% of all deaths Effective chemotherapeutic agents simply do not exist Too costly for much of the population to afford Developed countries only 4% to 8% Vaccines thus have become the most important tool for fighting infectious diseases in those parts of the world  RECOMBINANT AND SYNTHETIC VACCINES Widespread use of vaccination Smallpox vaccine Diphtheria – Corynebacterium diphtheriae Poliomyelitis Cost-efficiency - vaccination is much less costly than treating people who are already sick Vaccines continue to play an important role in veterinary medicine Farm animals are kept in tight quarters a practice that enormously increases the chances of cross-infection RECOMBINANT AND SYNTHETIC VACCINES RECOMBINANT AND SYNTHETIC VACCINES  PROBLEMS WITH TRADITIONAL VACCINES Traditional vaccines are of two types, live and killed Live vaccines consist of attenuated (weakened) viral or bacterial strains - prolonged storage or cultivation under suboptimal conditions Killed vaccines are either killed whole cells of bacteria or inactivated toxin proteins, which are called toxoids Many traditional vaccines are quite effective, but new vaccines, and new techniques for producing vaccines, are desperately needed  PROBLEMS WITH TRADITIONAL VACCINES For many important diseases, vaccines have not yet been developed Moreover, certain of the traditional vaccines are not sufficiently effective or are not entirely safe PROBLEMS WITH TRADITIONAL VACCINES  PROBLEMS WITH TRADITIONAL VACCINES Danger of reversion to the virulent state Have to be grown in tissue culture cells - hidden viruses Themselves can cause severe reactions “whole-cell” vaccine for pertussis - lipopolysaccharide (LPS), also called endotoxin Direct risk run by the workers May not be completely killed or inactivated Sufficient quantities is not always possible or affordable.  IMPACT OF BIOTECHNOLOGY ON VACCINE DEVELOPMENT Developments in biotechnology have led to the production of new kinds of vaccines Directed at new targets More effective or safer than traditional vaccines Protective antigen – a molecule that can produce specific immunity Either a traditional purification strategy or Recombinant DNA methods Antigen is produced in a safe, non-pathogenic organism such as Escherichia coli or yeast  IMPACT OF BIOTECHNOLOGY ON VACCINE DEVELOPMENT Recombinant DNA technology allows vaccines to be produced even when the pathogens are difficult or impossible to cultivate New vaccines contain only one or some of the molecules found in the original pathogen, they are often called subunit vaccines Acellular pertussis vaccine and conjugate polysaccaride vaccines – produced mostly by nonrecombinant DNA methods Hepatitis B subunit vaccine, which was developed through recombinant DNA technology.  ACELLULAR PERTUSSIS VACCINE Pertussis, or whooping cough, is a childhood disease Before the introduction of vaccine, accounted for 270,000 cases of illness resulting in 10,000 deaths annually in the United States The World Health Organization (WHO) - 45 million cases occur annually worldwide, with 400,000 deaths  ACELLULAR PERTUSSIS VACCINE This vaccine consists of Heat-killed,whole gram-negative cells of the causative organism, Bordetella pertussis Along with chemically inactivated culture supernatants Containing many toxic components It frequently causes adverse reactions Include fever, local redness, and swelling (which occur in nearly 50% of infants who receive injections  ACELLULAR PERTUSSIS VACCINE 1970s - the vaccine caused acute brain damage and sudden infant death - drastic decrease in the rate of immunization in Japan and Sweden - caused rapid increases in the occurrence of pertussis in these countries In response, Japanese scientists developed acellular vaccines, which contain chemically inactivated, purified pertussis toxin, accompanied by a few purified proteins of B. pertussis These preparations are effective, produce fewer adverse effects, and have attained public acceptance  ACELLULAR PERTUSSIS VACCINE The whole-cell vaccine decreased the number of cases dramatically in developed countries  ACELLULAR PERTUSSIS VACCINE Although preferable to the whole-cell vaccine, these acellular vaccines, developed before the advent of recombinant DNA technology, are in no way perfect. Chiron now produces a recombinant DNA–derived pertussis toxin vaccine (Europe) inactivated by the introduction of two specific alterations in its amino acid sequence destroy the toxic activity without altering the overall protein conformation ACELLULAR PERTUSSIS VACCINE  CONJUGATE POLYSACCHARIDE VACCINES Before effective vaccines - Haemophilus influenzae type b produced about 800 cases of “invasive disease” per 100,000 population per year Streptococcus pneumoniae produced about 200 cases per 100,000 population per year These organisms are the leading causes of bacterial infection in young children, often leading to invasive infections such as meningitis, pneumonia, and bacteremia  CONJUGATE POLYSACCHARIDE VACCINES In both, the protective antigen is the polysaccharide capsule Polysaccharides can produce effective immunity in adults, but not in infants  CONJUGATE POLYSACCHARIDE VACCINES When the purified polysaccharides are covalently linked to a “carrier” protein, the resulting conjugates function as very effective vaccines in infants  CONJUGATE POLYSACCHARIDE VACCINES The first of conjugate H. influenzae vaccines was licensed for immunization of infants in 1990, A conjugate pneumococcal vaccine was licensed in 2000 The H. influenzae type b vaccine - decreasing the invasive infection Some of these conjugate vaccines use a genetically inactivated version of diphtheria toxin called CRM197