VACCINOLOGY

VACCINOLOGY

• History• Concept of Vaccination

and Types of Vaccines• General Principles• Principles according to type• Practices• Present status of Vaccines

[update]

HISTORY

• Lady Mary Montagu was first to introduced

variolation in Great Britain- 1718

Edward Jenner

First to publish and test immunity by challenge with smallpox.

1796, inoculated a person, 5 years later vaccination became popular.

Invented smallpox vaccine

Dawn of Immunological Science

1875-1910Louis Pasteur

• 1881 anthrax vaccine was run and in 1882 85000 sheep was immunized.

• Introduced use of vaccinia virus

• Invented rabies vaccine

Robert Koch

• His discovery of Vibrio cholerae, killed

whole-cell bacterial vaccines were

introduced in 1896

Early Bacterial Vaccines, toxins, and toxoids [1910-1930]

• Koch’s isolation of tubercle bacillus, ushered the search for a vaccine for tuberculosis.

• 13 years after bacille Calmette-Guerin (BCG) was invented

• Calmette [left] Guerin [right]

• World War I gave increased opportunity for the killed whole-cell bacterial vaccines to make, especially in the case of typhoid.

• 1920s a killed bacterial vaccine was used fairly widely against Bordetella pertussis.

• 1923 Glenny and Hopkins discovered that formalin treatment of diphtheria toxin could render it harmless while preserving its immunogenic potential

Early Viral Vaccines: Yellow Fever and Influenza

[1930-1950]• Max Theiler’s safe and effective live

attenuated yellow fever vaccine 17D, hails from this period.

• First-generation killed whole-virus influenza vaccines and vaccines against typhus and Japanese B encephalitis vaccines also hails from this period.

The tissue Culture Revolution: Poliomyelitis, Measles, Mumps and

Rubella [1950-1970]• On April 12 1955, the 10th anniversary of the

death of Franklin Roosevelt, the famous polio victim, a press conference in the University of Michigan revealed to the world that Jonas Salk’s formalin-treated whole virus vaccine provided protection

• between 1955 and 1961, 300 million does were administered and incidence of polio declined dramatically

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• In 1965 Salk’s vaccine was replaced by Albert Sabin’s vaccine because 149 cases of polio occurred due to faulty production technique

• Edmondston strain of measles vaccines Enders’ original was first introduced in 1963 but was still risky

• 1964 more attenuated Moraten an Schwartz derivatives of the original Enders strain was introduced.

• 1967 mumps vaccine was invented• 1968 a live attenuated rubella vaccine was invented• 1969 a combined measles-mumps-rubella vaccine

was introduced and licensed in 1971

Dawn of the Molecular Era: Hepatitis B., Pneumococcus, and Haemophilus

influenzae B. [1970-1990]• Hepatitis B vaccine, use of the surface antigen of the

hepatitis B virus represented a new degree of purity of a single protein as a vaccine.

• First vaccine manufactured through recombinant DNA technology.

• First time vaccine was introduced as a expensive vaccine for special risk groups like doctors, nurses etc.

• Ushered in the new era where genetic engineering approaches have become the norm in vaccine research and development.

• Molecular vaccines of a different character were the subunit capsular polysaccharide vaccines against Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae B were licensed in 1970s and early 1980s.

• Various Hib conjugates were licensed in the late 1980s effectively bringing us to the modern era

Small pox eradication

• By 1953 North and Central America had beaten it• 1953 Europe• 1975 eliminated in Asia• Last occurring case recorded in Merca Somalia on

October 26, 1977• December 9, 1979, the Global Commission

certified that eradication was achieved.• An estimation of U.S. $300 million over 11 year

period was spent.

Concept of vaccination and Types of Vaccine

• To stimulate the immune response without subjecting an individual to the risk of actual infection.

• Primarily to prevent infection

• Strengthen an immune response that is inadequate, particularly in chronic recurrent diseases

• Types of vaccines• live attenuated

vaccine• Inactivated vaccine• Polysaccharide

vaccines • Recombinant vaccines

General principles• Another way to produce active immunity is by

vaccination.

• Vaccines interact with the immune system and often produce an immune response similar to that produced by the natural infection

• do not subject the recipient to the disease and its potential complications.

• Vaccines produce immunologic memory similar to that acquired by having the natural disease.

• Many factors may influence the immune response to vaccination.These include the presence of maternal antibody, nature and dose of antigen, route of administration, and the presence of adjuvants

Principles according to type. 1. Live Attenuated Vaccines

• Live vaccines are derived from “wild,” or disease-causing, virus or bacteria. These wild viruses or bacteria are attenuated, or weakened, in a laboratory, usually by repeated culturing

• In order to produce an immune response, live attenuated vaccines must replicate (grow) in the vaccinated person. A relatively small dose of virus or bacteria is given, which replicates in the body and creates enough virus to stimulate an immune response.

• The immune response to a live attenuated vaccine is virtually identical to that produced by a natural infection

2. Inactivated vaccines

• These vaccines are produced by growing the bacteria or virus in culture media then inactivating it with heat and/or chemicals (usually in formalin).

• Inactivated vaccines are not alive and cannot replicate. The entire dose of antigen is administered in the injection. These vaccines cannot cause disease from infection, even in an immunodeficient person

• In general, the first dose does not produce protective immunity, but only “primes” the immune system. A protective immune response develops after the second or third dose

• the immune response to an inactivated vaccine is mostly humoral. Little or no cellular immunity results.

3. Polysaccharide vaccines

• are a unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria

• The immune response to a pure polysaccharide vaccine is typically T-cell independent, which means that these vaccines are able to stimulate B-cells without the assistance of T-helper cells.

Practices• Simultaneous administration

of antibody (in the form of immune globulin) and vaccine is introduced as Post exposure prophylaxis of certain diseases, such as hepatitis B,rabies, and tetanus.

• If the live vaccine is given first, the antibody is given at least 2 weeks after.

• Oral typhoid is not licensed for children less than 6 years of age

• Live parenteral (injected) vaccines (MMR, varicella, and yellow fever) that are not administered simultaneously are separated by at least 4 weeks

• If the antibody is given before a dose of varicella vaccine, Antibody is allowed to degrade before giving the vaccine to reduce the chance of interference by the antibody

• Simultaneous administration of all vaccines for which a child is eligible is very important in childhood vaccination programs, it increases the probability that a child will be fully immunized at the appropriate age

Vaccine Update

• Under-used vaccines– Haemophilus influenzae

type b• By end of 2002, 100% of

countries were using the vaccine in routine immunization programme

– Hepatitis B• By 2001 only 75% of

countries have this vaccine in their infant immunization routine

– Yellow fever• Avialable since 1937

but its used has been a public health failure. Over the past 2 decades there were 12 times as many cases as during the previous 2 decades

– Rubella• Universal rubella

immunization has not been recommended by WHO to date

Vaccine Update• Eradication of vaccine

preventable diseases– Polio

• Polio-free– 1994 Americas– 2000 western pacific– 2002 Europe

– Measles

• Still in progress• In 2001 over 100

million children have been vaccinated in Africa alone

– Neonatal tetanus• 104 out of 106

developing countries have succeeded.

• WHO, UNICEF and UNFPA set a joint effort to eliminate this disease by the end of 2005

Vaccine Update

• Priority new vaccines– HIV/AIDS

• No effective vaccine at present

– Malaria

• No effective vaccine at present

– Tuberculosis

• Limited protection, immunity is believed to wane during adolescence

– Pneumococcal disease– New vaccine was

licenced in 2000 United states. but not applicable foe developing countries due a different bacterial strain.

– Meningococcal disease• New licensed in 1999 for

a serogroup C disease– Rotavirus diarrhoea

• Development and testing going on

Vaccine Update• Neglected vaccines

– Cholera• Safe and effective are

available, but oral vaccine are under consideration for public health use in emergency situation to immunize population at high risk.

– Shigella dysentery• It is likely to be 5-10

years before a vaccine is introduced.

– Dengue• 2 vaccines are

undergoing trials 1 being developed in the United States the other in Thailand

– Japanese encephalitis• A vaccine has been

developed and tested in china but not yet suitable for global use.

– Leishmaniasis• Development remains

fragmented and lacks support

– Schistosomiasis• Two leading candidates

have been successful in animals 1 has advanced to human trials.

Vaccine Update• Other vaccines

– Cervical cancer• The most advanced

candidates in development are recombinant protein vaccine against HPV types 16 and 18. Which could prevent 50-60% of cervical cancer.

– Respiratory syncytial virus• Current vaccine efforts

are directed toward the development of a vaccine that incorporates the 2 RSV serotypes [A and B]

– Herpes simplex virus type 2

– Enterotoxigenic Escherichia coli [ETEC]

• A new vaccine delivery technology-transcutaneous immunization involving the use of patch to deliver vaccine through skin, has been successfully tested in humans for ETEC vaccine