Immunizations

Which line of defense do vaccines work on?

Third (adaptive) line of defense - Consists of T and B lymphocytes. Acts slowly, mounting an antigen specific response and creating a immunological memory

What is the second line of defense?

Consists of phagocytes that are able to mount a rapid and non specific response to PAMPs

What is the first line of defense?

Consists of physical barriers (skin, mucosal membranes) and normal flora

What are antigens?

Components of pathogens that trigger an immune response as the body recognizes it as a foreign entity

What are epitotes?

3D shaped regions on antigens which the body's immune system recognizes to mount an immune response

How does an antigen cause an immune response?

The antigen is recognized by APCs, which presents it to t cells within lymph nodes via MHC 2. The t cell differentiates into cytotoxic and t helper cells, the later of which stimulates B cells to produce antibodies and create memory B cells that builds on the body's immunological memory

What are 4 ways in which antibodies destroy pathogens?

Neutralization - Antibodies bind to toxins or adhesion molecules on pathogens, preventing the pathogen from causing an infection

Opsonization - Antibodies, specifically IgG, have receptors that allow neutrophils and macrophages to bind to tagged pathogens

Agglutination - Antibodies can bind to multiple pathogens due to having two binding sites, allowing them to aggregate the pathogens and form a pathogen clot, which impairs its infective capabilities and increases its chance of being filtered from the blood by the spleen due to its larger size

Cytotoxicity - Antibodies can bind to an NK cell and pathogen, which causes the pathogen to be destroyed through perforin and granzyme produced by the NK cell

What are 4 types of antibodies?

IgM (initial immune response)

IgG (extracellular immune response, can leave blood vessels and kill of pathogens before it is systemic, can cross placenta)

IgA (Mucosal membrane immune response, can transfer vis breast milk via mammary glands)

IgE (Allergic + parasitic immune response)

Which antibody is responsible for naturally acquired passive immunity in fetuses?

IgG -> can cross placenta

Which antibody is responsible for naturally acquired passive immunity in breastfeeding infants?

IgA -> can be passed from breastmilk

What are the 4 types of acquired immunity?

Naturally acquired active immunity (infection -> immunity)

Naturally acquired passive immunity (placenta, breast milk)

Artificially acquired active immunity (vaccine)

Artificially acquired passive immunity (preformed antibodies)

What is naturally acquired active immunity?

Immunity acquired from the body's response to antigen exposure from an infective pathogen

Results in production of memory B cells that confer long term immunity

What is naturally acquired passive immunity?

Immunity acquired from fetus/newborns from the placenta (IgG) or from breast milk (IgA)

Confers instant temporary immunity

What is artifically acquired active immunity?

Immunity acquired from the body's immune response to vaccines

Results in production of memory B cells that confer long term immunity

What is artificially acquired passive immunity?

Immunity acquired from receiving preformed antibodies

Confers instant temporary immunity

What is the difference of active and passive immunity?

Active immunity involves the production of memory B cells after the immune system mounts a response to a pathogen or associated antigen. It takes a few days to develop but results in long term immunity.

Passive immunity involves receiving preformed antibodies, either artificially or naturally via breast milk or the placenta. It confers instant immunity but only lasts temporarily.

What are 4 types of vaccines?

1. Attenuated Vaccines - weakened version of pathogen

2. Inactivated Vaccines - killed pathogen

3. Subunit Vaccines - component of pathogen

4. Toxoid Vaccines - contains toxin

What is the most "effective" type of vaccine?

Attenuated vaccines - contains weakened version of pathogen that is still able to replicate, which allows for immune contact of many epitopes. Usually allows for lifelong immunity after 1 to 2 doses

What are attenuated vaccines?

aka modified live vaccine

Vaccines that contain a live weakened version of a pathogen that is still capable of replicating, allowing for immune contact of many antigens that elicits a vigorous immune response. This makes attenuated vaccines extremely effective, allowing for lifelong immunity after 1 to 2 doses

Which patient populations are attenuated vaccines cautioned for?

Immunosuppressed individuals

Pregnant individuals (esp MMR -> can cause direct fetal harm if it crosses the placenta)

These populations should either receive the vaccine at a later time (after pregnancy) or take inactivated/subunit vaccines

What are inactivated vaccine?

aka killed vaccines

Vaccines that contain an inactivated or killed version of the pathogen, that does not retain any residual virulence, which results in less antigen exposure compared to attenuated vaccines. This makes inactivated vaccines less effective than attenuated vaccines, and requires multiple doses + boosters to confer full immunity

What are subunit vaccines?

Vaccines that contain a piece of the pathogen that is dense in antigens. Similar to inactivated vaccine, they are less effective that attenuated vaccines due to lower antigen exposure, and require multiple doses + boosters to confer full immunity

What are toxoid vaccines?

Vaccines that contain deactivated toxins produced by a target pathogen. Similar to inactivated vaccines, they contain fewer antigens compared to attenuated vaccines, and require multiple doses + boosters (~10 yrs) to confer full immunity

What is the difference in adaptive immune response during a primary and secondary response to a pathogen/antigen?

During the primary response, the adaptive immune system is slow to be activated, with predominant IgM involvement followed by IgG involvement. It is often preceded by a 3 day lag period for the immune system to be activated. The pathogen often takes weeks to fully be cleared from the system.

During the secondary response, the adaptive immune system is immediately activated with IgG and IgM production as it does not rely on APC presentation to recognize the antigen, resulting in rapid production of large amounts of antibodies, which can neutralize the pathogen within a few days

What are viral vector vaccines?

Vaccines that use viruses as a vector to inject genetic code for an antigen from a target pathogen into the host cell, resulting in a immune response to the antigen and developing artificial active immunity

What are mRNA vaccines?

Vaccines that directly inject mRNA genetic code that encodes for a target pathogen into a host cell, resulting in a immune response to the antigen and developing artificial active immunity

What are vaccine adjuvants?

Additional substances inserted into a vaccine that "wake up" the innate immune system, specifically APCs and antigen presentation signals, so that the immune system can mount a stronger response to the antigen.

This allows for fewer required vaccine doses, antigens per dose, and improves vaccine response in older adults with weaker immune systems

What are benefits of vaccine adjuvants?

Allows for fewer required vaccine doses, antigens per dose, and improves vaccine response in older adults with weaker immune systems

When should artificially passive immunization be considered over active immunization?

-Unavailable or contraindicated vaccines (pregnant, young infants)

-Unvaccinated individual is exposed to the pathogen and requires immediate protection (active immunity takes weeks to develop)

What are immunization strategies for RSV?

Subunit vaccine "ABRYSVO"

Passive immunotherapy "BEYFORTUS"

When should an active vaccine be used for RSV protection?

-High risk older adults

-Pregnant people who are expected to deliver shortly during RSV season via IgG antibodies which are passed through the placenta to the newborn (ideally 2 week before pregnancy)

When is "RSV" season?

Fall through spring

Generally November - March

When should passive immunotherapy be used for RSV protection?

Infants experiencing their first RSV season or infants with ongoing risk during second RSV season as active vaccines are contraindicated and the vaccine is able to provide protection immediately and for 5 months

How should SUBQ and IM vaccines be administered?

Administer to deltoid region or anterolateral surface of thigh for <1 yr infants.

Remember to clean the injection area with an antiseptic to avoid introducing normal flora into the body

How should vaccines be stored?

Should be stored within 2C - 8C from the time of manufacture until the vaccine is administered (cold chain)

Ideally, the vaccine should be stored in large refrigerators at the center and should be checked with a themometer twice per day

How should multidose vials be stored?

Should be documented with first initial use, and should be returned to the refrigerator immediately after use

What is thimerosal and how is it used for vaccines?

Thimerosal is a chemical that contains mercury which is added to prevent serious infections caused by bacterial or fungal contamination of the vaccine (normal flora)

Most Canadian vaccines do not contain thimerosal and those that do contain well below the tolerable daily intake for both adults and infants (you consume more mercury from eating fish)

What are vaccine contraindications?

Situations where vaccines should not be used due to risks outweighing potential therapeutic benefits. Consider past immunization experiences, allergies, close contacts who may be affected by use, and current health status

What are vaccine precautions?

Situations where vaccines may increase the risks of adverse effects or may compromise the ability of the vaccine to provide immunity. The vaccine is often deferred unless if the benefits outweigh any potential risks

Can individuals with mild illness still have vaccines?

Yes, there is no increase risk of adverse effects

What are adverse events following immunizations?

Unwanted or unexpected health effects that occur after a vaccine which may or may not be caused by the vaccine

What are common adverse effects of immunizations?

Local inflammation reaction (soreness at site <4 days)

Systemic inflammation reactions (fever, headache, muscle ache)

Predictable and self limiting

What are 7 types of adverse events following immunizations?

Vaccine product related reaction (caused by vaccine)

Vaccine product defect related reaction (caused by defective vaccine)

Immunization error related reaction (caused by error in 6 rights of adminstration)

Immunization triggered stress response (caused by anxiety of vaccine)

Coincidental event (not caused by vaccine)

Serious AEFI (life threatening adverse effect)

Unexpected AEFI (not consistent with expected adverse reactions)

What is a vaccine product related AEFI?

Adverse reaction caused by inherent properties of the vaccine product ; expected reaction

What is a vaccine product defect related AEFI?

Adverse reaction caused by quality defects of the vaccine product

What is an immunization erorr related AEFI?

Adverse reaction caused by inappropriate usage of the vaccine ; preventable (6 rights of administration)

What is an immunization triggered stress AEFI?

Adverse reaction caused by anxiety about the immunization

What is a coincidental AEFI?

Adverse reaction caused by something other than the vaccine that just so happens to occur after the vaccine is administered

What is a serious AEFI?

Adverse reaction that is life threatening, requires hospitalization, causes disability or causes a congenital/birth defect

What is an unexpected AEFI?

Adverse reaction that is not consistent with the effects listed by the product monograph; not expected adverse reaction

What are 4 general benefits of vaccines?

Reduces hospitalizations from severe disease

Cost effectiveness

Eradication of diseases

Provides herd immunity

What is herd immunity?

Immunity of an entire population, including those who cannot get vaccinated, when a large proportion of the population is resistant from active immunity

Typically the resistant threshold is >75% of the population. For measles it is >95% of the population