Question

Your goal is to design a vaccine that will protect vaccinated individuals from disease caused by the infectious agents listed below. This does not always mean you need “sterilizing immunity” (protection from infection), although in some cases this might be your goal.

Tetanus: Tetanus is caused by an infection with the bacterium Clostridium tetani, commonly found in soil, dust, and manure. Spores of the C. tetani can remain infectious for more than 40 years. You can get tetanus when the spores enter your body through an injury or wound, especially via a contaminated object. C. tetani produces a toxin that interferes with muscle contractions, resulting in the symptoms that can lead to permanent contraction (lockjaw) and death. The agent does not spread between people.

1- Key Pathogen Features:

2- Population & Location Factors:

3- Immunologic Goals:

4- Vaccine Strategy:

5- Test to evaluate effectiveness:

Answer 1

1- Key Pathogen Features:

Tetanus: Tetanus or lock jaw disease is caused by an infection with the bacterium Clostridium tetani, commonly found in soil, dust, and manure. Spores of the C. tetani can remain infectious for more than 40 years. You can get tetanus when the spores enter your body through an injury or wound, especially via a contaminated object. C. tetani produces a toxin that interferes with muscle contractions, resulting in the symptoms that can lead to permanent contraction (lockjaw) and death. The agent does not spread between people.

Clostridium tetani is a a rod-shaped, Gram-positive common soil bacterium typically up to 0.5 μm wide and 2.5 μm long. However, when forming spores, C. tetani becomes substantially enlarged at one end, resembling a tennis racket or distinctive drumstick shape. Upon exposure to various conditions, C. tetani can shed its flagella and form a spore. These spores are extremely hard and are resistant to heat, various antiseptics, and boiling for several minutes. When exposure to wound, the spores enter into our body they can grow and produce a potent neurotoxin, tetanospasmin, which interferes with motor neurons, causing tetanus. C. tetani spores are long lived and found globally in soil or in the gastrointestinal tract of various livestock and companion animals.

2- Population & Location Factors:

Tetanus is a worldwide neurological disease of man and animals, characterized by spastic paralysis of skeletal muscles. Tetanus has 4 different clinical manifestations:

i) Local tetanus at the site of injury;

ii) Cephalic tetanus: Cephalic tetanus occurs due to head injuries or infections.

iii) Generalized tetanus: Generalized tetanus is the most common and represents 80% of the tetanus cases.

iv) Neonatal tetanus: Neonatal tetanus occurs in infants within 28 days of birth, due to infection of the umbilical stump.

Tetanus in developed countries is low and has been declining due to effective vaccination programs. According to US Centers for Disease Control and Prevention (CDC) one million cases of tetanus occur each year, worldwide, with approximately 300,000-500,000 deaths. The World Health Organization (WHO) estimates approximately 34,000 neonates died from neonatal tetanus. Tetanus, however, is still very common in the developing countries, with mortality rates exceeding 50%.

3- Immunologic Goals:

In 1897, Edmond Nocard, a French veterinarian and microbiologist showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. There is an increase in the production of tetanus antitoxin in the immunized animals which delayed the development of hypersensitivity and the activation of the mechanisms of cell-mediated immunity. In non-immunized animals there is a specific change in the T-system of immunity without the appearance of the clinical symptoms of tetanus, which is, probably, one of the mechanisms of natural immunity.

4- Vaccine Strategy:

Tetanus Toxoid vaccines are made by purifying the bacterial exotoxin. Toxicity of purified exotoxins is then suppressed or inactivated either by heat or with formaldehyde to form toxoids. Vaccination with toxoids induces anti-toxoid antibodies that are able to bind with the toxin and neutralize its deleterious effects. The production of toxoid vaccines is strictly controlled to maintain immunogenecity without excessive modification of the antigenic epitope structure. Such “detoxified” toxins are safe to use as vaccines. When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin. The immune system produces antibodies that opsonize the bacterial toxins.

The introduction of a tetanus toxoid (TT) vaccine has greatly reduced its incidence in developed and developing countries. Vaccination with bacterial toxoid vaccination and adjuvants is the best way to prevent the spread of tetanus. The tetanospasmin toxin's action can be prevented with TT vaccines, which are often administered to children worldwide. To increase immunogenicity, TT is formulated with aluminum or calcium salts and administered by intramuscular injection. TT vaccines are produced in two forms, either as a single form of antigenic vaccine (TT) or in combination with diphtheria toxoid (DT), or mixed with diphtheria and whole cells or cellular pertussis (DTP).

The tetanus vaccine is routinely given to children as part of the diphtheria and tetanus toxoids and acellular pertussis (DTaP) shot. The DTaP vaccine consists of five shots, usually given in the arm or thigh of children when they are aged 2 months, 4 months, 6 months, 15 to 18 months and 4 to 6 years. A booster is normally given between the ages of 11 and 18 years, and then another booster every 10 years. If an individual is traveling to an area where tetanus is common, they should check with a doctor regarding vaccinations. Anyone who receives a deep or dirty wound and has not had a booster shot over the last 5 years should have another booster. In this situation a patient may also be given tetanus immune globulin, which works to prevent infection. It is important that medical attention is sought swiftly as tetanus immune globulin only works for a short time after the injury.

5- Test to evaluate effectiveness:

After administration of tetanus vaccine the antitoxin levels decrease with time. While some persons may be protected for life, by 10 years after the last dose, most persons have antitoxin levels that only approach the minimal protective level. As a result, routine boosters are recommended every 10 years. In a small percentage of individuals, antitoxin levels fall below the minimal protective level before 10 years have elapsed. To ensure adequate protective antitoxin levels, persons who sustain a wound that is other than clean and minor should receive a tetanus booster if more than 5 years have elapsed since their last dose.