Vaccine & Vaccination

1. Vaccine & Vaccination Ibrahim A. Alsarra, Ph.D. Professor of Pharmaceutical Biotechnology King Saud University College of Pharmacy Departments of Pharmaceutics/ Pharmacognosy PHG 424: Pharmaceutical Biotechnology

2. Outlines • Historical Background • Introduction • Types of Vaccines • Immunological Principles • Vaccination Schedule • Concluding Remarks

3. Vaccines • A vaccine is an antigenic preparation used to establish immunity to a disease. The term derives from Edward Jenner's use of cowpox ("vacca" means cow in Latin), which, when administered to humans, provided them protection against smallpox, which Pasteur and others perpetuated. • The process of distributing and administrating vaccines is referred to as vaccination. • Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated).

4. History • Long before the causes of disease were known and long before the processes of recovery were understood, an interesting thing was observed: if people recovered from a disease, they appeared to be immune from a second infection with the same illness. • Perhaps it was these types of observations that led the Chinese to try to prevent smallpox--a deadly disease characterized by pus-filled blisters--by exposing uninfected individuals to matter from smallpox lesions. This process, known as "variolation“.

5. History…cont. • One form consisted of removing pus and fluid from a smallpox lesion and using a needle to place it under the skin. • Second method: involved peeling scabs from lesions, drying and grinding them to a powder, and letting an uninfected person inhale this powder. • The third method involved picking up a small amount of the scab powder with a needle and then using the needle to place the powder directly into the individual's veins.

6. History…cont. • One person who experienced variolation as a child in the late 1700s was Edward Jenner, a young boy who survived the process and grew up to become a country doctor in England. • As a country doctor, Jenner noticed a relationship between the equine disease known as "grease" and a bovine disease known as "cow pox.“ • Unlike lethal smallpox, however, the cowpox blisters eventually disappeared, leaving only a small scar at the site of each blister.

7. History…cont. • At the same time, Jenner was interested when a milkmaid told him that she could not catch smallpox because she had cowpox. Jenner noted that there were many people like the milkmaid - people who milked cows and who did not get smallpox even when exposed repeatedly. • With this in mind, Jenner undertook an experiment in 1796: he infected a young boy with cowpox in hopes of preventing subsequent smallpox infection. • After allowing the boy to recover fully from cowpox, Jenner - in an experiment that would be considered unethical by today's scientific community - intentionally infected the boy with smallpox by injecting pus from a smallpox lesion directly under his skin.

8. Introduction The ideal vaccine: • 100% efficient in all individuals of any age. • Provides lifelong protection after single administration. • Does not evoke an adverse reaction. • Stable under various conditions (Temp., Light,...etc.). • Easy to administer, preferably orally. • Available in unlimited quantities. • Cheap.

9. Introduction…cont. • Disease causing organisms have at least two distinct effects on the body: • The first effect is very obvious: we feel sick, exhibiting symptoms such as fever, nausea, vomiting, diarrhea, rash, and many others. • Although the second effect is less obvious, it is this effect that generally leads to eventual recovery from the infection: the disease causing organism induces an immune response in the infected host. • As the response increases in strength over time, the infectious agents are slowly reduced in number until symptoms disappear and recovery is complete.

10. Introduction…cont. • How does induction of the immune response occur? • The disease causing organisms contain proteins called "antigens" which stimulate the immune response. The resulting immune response is multi-fold and includes the synthesis of proteins called "antibodies." These proteins bind to the disease causing organisms and lead to their eventual destruction. In addition, "memory cells" are produced in an immune response.

11. Introduction…cont. • These are cells which remain in the blood stream, sometimes for the life span of the host, ready to mount a quick protective immune response against subsequent infections with the particular disease causing agent which induced their production. • If such an infection were to occur, the memory cells would respond so quickly that the resulting immune response could inactivate the disease causing agents, and symptoms would be prevented. • This response is often so rapid that infection doesn't develop - you are immune from infection.

12. Types of Vaccines • Vaccines may be living, weakened strains of viruses or bacteria that intentionally give rise to unapparent-to-trivial infections. • Vaccines may also be killed or inactivated organisms or purified products derived from them. Vaccines: can be divided into: Traditional Vaccines Innovative Vaccines

13. Types of Vaccines…cont. There are four types of traditional vaccines: • Inactivated: these are previously virulent micro-organisms that have been killed with chemicals or heat. Examples are vaccines against:flu, cholera, plague, and hepatitisA. Most such vaccines may have incomplete or short-lived immune responses and are likely to require booster shots. • Live, attenuated: these are live micro-organisms that have been cultivated under conditions that disable their virulent properties. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include:yellow fever, measles, rubella, and mumps.

14. Types of Vaccines…cont. • Toxoids: these are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include: tetanus and diphtheria. • Subunit: rather than introducing a whole inactivated or attenuated micro-organism to an immune system, a fragment of it can create an immune response. Characteristic example is the subunit vaccine against HBV that is composed of only the surface proteins of the virus (produced in yeast).

15. Types of Vaccines…cont. A number of innovative vaccines are also in development and in use: • Conjugate: certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilusinfluenzae type B vaccine. • Recombinant Vector: by combining the physiology of one micro-organism and the DNA of the other, immunity can be created against diseases that have complex infection processes.

16. Types of Vaccines…cont. • DNA vaccination - in recent years a new type of vaccine, created from an infectious agent's DNA called DNA vaccination, has been developed. It works by insertion (and expression, triggering immune system recognition) into human or animal cells, of viral or bacterial DNA. • Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. • One advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is still experimental, but shows some promising results.

18. Immunological Principles • After a natural infection the immune system in most cases launches an immunological response to the particular pathogen. • The immune system recognizes vaccine agents as foreign, destroys them, and 'remembers' them. When the virulent version of an agent comes along, the immune system is thus prepared to respond, by: (1)- neutralizing the target agent before it can enter cells, and: (2)- recognizing and destroying infected cells before that agent can multiply to vast numbers.

19. Immunological Principles…cont. • After recovery from the disease, the immunological response protects us from that disease. This phenomenon is called immunity and is due to the presence of circulating antibodies, activated cytotoxic cells and memory cells. • The principles of vaccination is mimicking an infection in such a way that the natural specific defense mechanism of the host against the pathogen will be activated, but the host will remain free from the disease that normally results from a natural infection.

20. Immunological Principles…cont. • Vaccination is also referred to as active immunization, because the host’s immune system is activated to respond to the infection. • Administration of specific antibodies can be utilized for short-lived immunological protection of the host. This term is known as passive immunization. • Traditionally, active immunization has mainly served to prevent infectious diseases, whereas passive immunization has been applied for both prevention and therapy of infectious diseases.

21. Vaccination schedule • In order to provide best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional 'booster' shots often required to achieve 'full immunity'. • This has led to the development of complex vaccination schedules. In the United States, the Advisory Committee on Immunization Practices, which recommends schedule additions for the Center for Disease Control, recommends routine vaccination of children against: hepatitis A, hepatitis B, polio, mumps, measles, rubella,diphtheria, pertussis, tetanus, chicken pox, influenza, meningococcal disease and pneumonia.

22. Vaccination schedule…cont. • The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. • Besides recommendations for infant vaccination boosters, many specific vaccines are recommended for repeated injections throughout life: most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. • Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group.

26. Efficacy of vaccines • Vaccines do not guarantee complete protection from a disease. Even after a vaccination, there is still a possibility that a vaccinated person may get the disease. • Sometimes this is because the host's immune system simply doesn't respond adequately or at all. This is known as a 'low titre of antibodies'. • This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or just bad luck (the host's immune system does not have a B-cell capable of generating antibodies to that antigen).

27. Efficacy of vaccines…cont. The efficacy or performance of the vaccine is dependent on a number of factors: • The disease itself (for some diseases vaccination performs better than for other diseases). • The strain of vaccine (some vaccinations are for different strains of the disease). • Whether one kept to the timetable for the vaccinations. • Some individuals are 'non-responders' to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly.

28. Efficacy of vaccines…cont. • Even if the host develops antibodies, the human immune system is not perfect. Some germs can mutate (the common cold and influenza viruses are highly efficient at this), and in any case the immune system might still not be able to defeat the infection. • Adjuvant is typically used to boost immune response.

29. Vaccine Controversies • A number of vaccines, including those given to very young children, have contained thimerosal,a preservative that metabolizes into ethyl mercury. It has been used in some influenza, DTP (diphtheria, tetanus and pertussis) vaccine formulations. • Since 1997, use of thimerosal has been gradually diminishing in western industrialized countries after recommendations by medical authorities, but trace amounts of thimerosal remain in many vaccines and in some vaccines, thimerosal has not yet been phased out despite recommendations. • Some states in USA have enacted laws banning the use of thimerosal in childhood vaccines.

30. Preservatives • In order to extend shelf life and reduce production and storage costs, thimerosal, a preservative containing about 49% of a form of mercury called ethyl mercury, was used routinely until recent years. • Thimerosal has been phased out in the U.S. in all but a few flu vaccines (it has been phased out in other countries, e.g. Denmark in 1992), but may be used in stages of manufacture.

31. Storage • Depending on their specific characteristics, vaccines are stored in solution or in a freeze dried formulation, usually at 2 – 8 ºC. • The shelf-life depends on the physicochemical characteristics of the vaccine formulation and on the storage conditions, and typically in the order of several years.

32. Recommended Sites • List of Vaccines Approved for Use in the United States: http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm • List of Vaccines Approved for Use in the Saudi Arabia: http://www.moh.gov.sa/des/sections.php?CatParent=29&CatID=36

33. Concluding Remarks

34. Remark: • There are still many viral and parasitic diseases against which no effective vaccines exist. • In addition, the growing resistance antibiotics increases the need to develop vaccines against common infections.