Immunology – handling – storage of vaccines

An understanding of basic immunology is needed to understand the mode of action of vaccines and the basis of recommendations for their use.

There are two basic mechanisms for protection against infection ( immunity).

• Active: the protection that is produced by one’s own body
• Passive: the protection by products produced by animals or humans and transferred by an injection to another human.

Immune system:

This is a complex system of interacting cells  whose primary purpose is to identify a foreign substance (Antigens can be live ( virus or bacteria) or inactivated) and the production of protein molecules called antibodies to eliminate the foreign substance . This type of immunity is called HUMORAL immunity

The most effective immune response is in response to live antigen ( such as hepatitis B surface antigen that is easily recognized by the immune system.

Other material such as polysaccharide ( long chain of sugar molecules that make up the building blocks of the cell wall) are less effective antigens and produce a lower level of protection.

I general, antibodies offer specific immunity only against the antigen ( or disease) for which it was produced. Measles antibodies does not protect against influenza virus.

PASSIVE immunity:

Passive antibodies offer only temporary protection. The level will degrade over months.

Examples of such immunity include:

• The antibodies that are transmitted through the placenta from an mother to an infant will last for up to a year protecting against diseases such as measles, rubella, tetanus). The child will receive the same antibody profile as the mother.
• Blood products such as red cells- plasma products -immune globulin contain variable quantities of antibodies.

There are three major types and sources of passive antibodies use in medicine:

• Homologous pooled human antibody:

Known as Immune globulin, it is produced by pooling IgG fractionating antibodies from thousands of donors. It is used primarily for post-exposure prophylaxis for hepatitis A and measles.

• Homologous human hyper immune globulins:

Products that contain high titers of a specific antibody donated from plasma of humans with high levels of this particular antibody.

These products however also contain small amounts of other antibodies.

It is used primarily for post-exposure prophylaxis for hepatitis B – rabies-tetanus-varicella-respiratory syncital virus.

• Heterologous hyperimmune serum ( antitoxin);

Products from animals ( horses) containing only one antibody against one antigen. Used for the treatment of botulism and diphtheria. It is complicated by serum sickness reaction to horse protein.

ACTIVE immunity:

Characterized by the stimulation of the immune system to produce antigen-specific antibodies (humoral) and cellular immunity. This leads to immunity lasting for years if not life-long.

Two mechanism:

1.      Natural disease:

This immunity following natural disease leading to the production of certain cells ( memory B-cells) continue to circulate in the blood and in the bone marrow, leading to immunologic memory. Upon re-exposure to the natural disease antigen , these memory cells begin to replicate and produce antibodies very rapidly.

2.      Vaccination:

Vaccines simulate the natural disease leading to the same immunologic response without subjecting the recipient to the complication of the disease.

The response may be influenced by several factors such as:

• Age-
• Nutritional factors-
• Genetics-
• Coexisting disease-
• Known smokers-
• Route of administration presence of adjuvants ( aluminum)-
• Presence of maternal antibody-
• Nature and dose of antigen.

Classification of vaccines:

1.      Live attenuated

2.      Inactivated

1-Live attenuated vaccines are produced by modifying a disease-producing ( wild) virus or bacteria in a laboratory. In general the more similar vaccine is to the natural disease, the better the immune response to the vaccine. The organism is attenuated by repeated culturing( the measles vaccine was isolated in 1954 from a child needed 10 years of serial passage in tissue culture in order to transform it into a vaccine virus. Once given in a small dose the attenuated virus replicates in large enough volume to stimulate an immune response. Any damage to the live organism ( heat – light) – or the presence of circulating antibodies                         ( transplacental-transfusion) will interfere with the vaccine. They must be stored carefully.

Live vaccines rarely causes disease. If it does it is usually much milder than the natural disease.

In immune deficient persons ( AIDS- Leukemia- elderly) the live attenuated vaccine ( yellow fever) can cause severe or fatal reactions by uncontrolled replication of the virus. At time the live polio vaccine can revert to it’s pathogenic form.

Currently available live attenuated vaccines include:

Live viruses:

• MMR
• Polio
• Yellow fever
• Varicella

Live bacteria:

• BCG
• Oral typhoid

2- Inactivated vaccines:

These vaccines are produced by growing the bacteria or virus in culture media , then inactivating it with heat and or chemicals( formalin). In the case of fractional vaccines, the organism is further treated to purify only the components to be included in the vaccine( such as the polysaccharide capsule of pneumococcus).

Theses vaccines are not alive and cannot replicate or cause disease even in an immunodeficient person.

They are also not affected by circulating antibodies.

Inactive vaccines always require multiple doses. In general the first dose only primes the immune system and full protection develops after the second or third doses.

In contrast to live vaccines, in which the immune response closely resembles natural infection, the immune response to an inactivated vaccine is mostly humoral and little or no cellular immunity results.

Antibody titers against inactivated antigens fall over time and require “boosting”.

Whole cell vaccines: In some cases the whole cell may be needed to  develop a protective immune response. Whole cell bacterial vaccines are typically the most reactogenic ( cause the most adverse events).

Current Inactivated vaccines including whole cell viruses:

• Influenza
• Polio
• Rabies
• Hepatitis A
• Whole cell bacteria
• Pertussis
• Typhoid
• Cholera
• Plague

Fractional vaccines include subunits:

• Hepatitis B
• Influenza
• Acellular pertussis
• Typhoid Vi
• Toxoid ( diphtheria-tetanus-botulinum)

Pure Polysaccharides:

• Pneumococcal
• Meningococcal
• H.influenzae b,

Polysaccharide Conjugates

• H.Influenzae type b
• Pneumococcal

Polysaccharide vaccines

Are unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Pure polysaccharide vaccines are available for three diseases.

Pneumococcal disease

Meningococcal disease and H. Influenzae type b.

The immune response to these vaccines is T-cell independent ( able to stimulate B-cells without the assistance of T-helper cells.

T-cell independent antigens are not constantly immunogenic in children <2 years of age. For reasons that are still unclear( possibly immaturity of immune system), children do not respond to polysaccharide antigens.

Contrary to most inactivated protein vaccines,  repeated boosters do not increase the antibody titer. Also the immune response is mainly IgM mediated and very little IgG.

In late 1980’s the process of conjugation was shown to overcome these problems.

Conjugation changes the immune response from T-cell independent to T-cell dependent, leading to increased immunogenicity in infants and antibody booster response with multiple doses of the vaccine. (Menjugate vaccine)

Recombinant vaccines:

Vaccines antigens may be also be produced by genetic engineering technology.

Hepatitis B vaccines are produced by the insertion of a segment of the hepatitis B virus gene into the gene of a yeast cell. The modified yeast cell produces pure hepatitis B surface antigen when it grows.

Live typhoid vaccine Ty21a) is salmonella typhi bacteria that has been genetically modified to not cause illness.

Storage and handling of vaccine:

Ship according to manufacturer standards:

Insulated container at temps between 2 and 8degrees C- or frozen on dry ice-

• Train all staff personnel who are in contact with vaccines
• Review procedure storage guidelines every 6 months with staff.
• Have an emergency plans in case of power failure.
• Record dose and lot number of every used vaccine.
• Avoid opening door unless removing and storing  vaccines.
• Vaccine dedicated refrigerator- No food sign
• Only use modern freezer- frost free freezers.
• Refrigerate shipped vaccines immediately on reception.

• Store yellow fever-oral polio-varicella in freezer.
• Do not store vaccines in the door of refrigerator
• Protect MMR-varicella vaccines from light –
• Remove vaccines from refrigerator only when ready to administer.
• Rotate stock to avoid outdating.
• Don’t over stock to avoid outdating and wastage.
• Note exp. date on cartons.
• Keep expired vaccines or vaccines exposed to abnormal temperatures in a special container marked DO NOT USE.
• Make sure refrigerator is plugged at all times.
• Post  warning sign on refrigerator indicating not to unplug and that vaccines are being stored.
• Contract alarm/security firm who will notify you of power failure.
• Lock refrigerator or keep room locked  to avoid tampering.
• Maintain temp of refrigerator  between 2 and 8degree C and freezer at                 -14 degree C or lower.
• Place water bottles in door and frozen  cold packs in freezer.
• Check and record temps twice a day.
• Monitor temps with high/ low electronic thermometer.

Disposal:

Dispose of all outdated or damaged vaccines by returning to manufacturer.

Dispose of used vaccines and syringes in “sharps” biohazard container to be disposed by licensed biohazard waste company.

Dr. Paul Assad