5.14 immunoprophylaxis immunotherapy

8/19/2019 5.14 Immunoprophylaxis Immunotherapy

1/60


2/60

Immunization

• - is one of the greatest public healthachievements;

• - is one of the few cost-saving

interventions to prevent infectiousdiseases;

• - is the principal factor contributing to thereduction of morbidity and mortalityaround the world.


3/60


4/60


5/60


6/60

Vaccination and immunization • Vaccination = immunization?

• Vaccination denotes only the

administration of a vaccine.• Immunization describes the process of

inducing or providing immunity by any

means, whether active or passive.• Vaccination does not guarantee

immunization.


7/60

Active and passive

immunization• Active immunization refers to the induction of

immune defenses by the administration of antigens

in appropriate forms.

• Passive immunization involves the provision of

temporary protection by the administration of

exogenously produced immune substances.


8/60

Definitions of Immunizing Agents I

• Vaccine – a substance that stimulates an

immune response that can either prevent aninfection or create resistance to an infection.

• No vaccine is 100% effective (most are 70-95%), no vaccine is 100% safe.


9/60

Definitions of Immunizing Agents II

• Toxoid - a modified bacterial toxin thathas been made nontoxic but retains thecapacity to stimulate the formation of

antitoxin.


10/60

Definitions of Immunizing Agents III

• Immune globulin - an antibody-containing

protein fraction derived from human plasma

and used primarily for maintenance of the

immunity of persons with immunodeficiency

disorders or for passive immunization whenthere is no opportunity for active immunization.

• Antitoxin - an antibody derived from the serum

of animals after stimulation with specific

antigens and used to provide passive immunity

to the toxin protein to which it is directed.


11/60


12/60

The generations of vaccines

• The first generation of vaccines:

– included whole killed bacteria,

– partially purified microbial products that induced protective

antibodies (e.g., diphtheria toxoid),

– live attenuated microorganisms.

• The second generation of vaccines has taken advantage of

molecular genetics and protein chemistry:

– purified proteins or subunits of organisms have been isolated and

manipulated,

– genetically engineered and attenuated live native organisms have

been generated, as have cloned antigens expressed by harmlessvector organisms.

• The third generation of vaccines:

– in which nucleic acids are used to induce immunity.


13/60

The types of vaccinesLive

Attenuatedvaccines

Killed

Inactivatedvaccines

Toxoids Cellular fractionvaccines

(Subunit vaccines)

Recombinantvaccines

•BCG•Measles

•Mumps

•Rubella

•Varicella•Intranasal

Influenza

•Typhoid oral

•Yellow fever•Oral polio

•Intra-muscular

influenza

•Polio

•Pertussis

•Rabies

•TBE

•Japaniseencephalitis

•Typhoid

•Cholera

•Hepatitis A

•Diphtheria•Tetanus

•Meningococcalpolysaccharide

vaccine(N.meningitidis A, C,Y, W-135)

•Pneumococcalpolysaccharidevaccine(S.pneumoniae 23valent adult,S.pneumoniae 7, 13valent pediatric)

•Acellular B. pertussis

•Hepatitis Bvaccine


14/60

Live attenuated vaccines• - consisting of selected or genetically altered organisms that are avirulent

or attenuated, but remain immunogenic, generally produce long-lasting

immunity (e.g. measles, mumps).

• These agents are expected to cause a subclinical illness and immunologic

response mimicking natural infection.

• They offer the advantage of replication in vivo, which increases the

antigenic load presented to the host’s immune system.

• They may confer lifelong protection with one dose.• They present all expressed antigens, thus overcoming immunogenetic

restrictions in some hosts.

• They may reach the local sites most relevant to the induction of protective

immunity.


15/60

Live attenuated vaccines

• Despite their advantages, live vaccines are not always

preferable.

• For example, live oral vaccines are contraindicated for

use in children and adults with immune deficiency

diseases.


16/60

Live attenuated viral vaccines• Polio (oral vaccine)

• Measles, mumps, rubella

• Yellow fever

• Varicella


17/60

Inactivated vaccines• - typically require multiple doses and periodic boosters

thereafter for the maintenance of immunity.

• Nonviable vaccines administered parenterally fail to

elicit mucosal IgA-mediated immunity, as they lack a

delivery system that can effectively transport them to

local antigen processing cells.

• However, killed vaccines can be extremely successful(the nonviable HepA vaccine appears to be close to

100% effective in inducing protective immunity).


18/60

Inactivated vaccines

• Currently available nonviable vaccines consist

of:

– inactivated whole organisms (e.g., pertusis vaccine); – detoxified protein exotoxins (e.g., tetanus toxoid);

– recombinant protein antigens by use of genetic

engineering (e.g., HepB vaccine);

– carbohydrate antigens present as soluble purified

capsular material (e.g., Streptococcus pneumoniae

polysaccharides)

– conjugated to a protein carrier (e.g., pneumo

conjugated vaccine ).


19/60

• Subunit vaccines use only those antigenicfragments of a microorganism that best stimulate animmune response.

• Recombinant vaccines are subunit vaccinesthat are produced by genetic modification techniques,meaning that other microbes are programmed toproduce the desired antigenic fraction.

– the vaccine against the hepatitis B virus consists of aportion of the viral protein coat that is produced by agenetically modified yeast.

Inactivated vaccines


20/60


21/60

Disadvantages of DNA Vaccines

• Potential risk of integration of viral genes from the vector;• Tumor promotion from integration near proto-oncogenes or

tumor suppressor genes;

• Possible induction of tolerance or autoimmunity by vaccine

persistence;

• Possible influence of strong promoters on expression of host

genes, with adverse consequences.


22/60


23/60

Route of administration

• Vaccines must be administered by the licensed route to ensureimmunogenicity and safety.

– administration of vaccine into the gluteal rather than the deltoid muscle

often fails to induce an adequate immune response, – subcutaneous rather than intramuscular administration of vaccine

increases the risk of reactions.


24/60


25/60

Adjuvants

Adapted from Corradin G, Del Giudice G. Curr Med Chem. 2005;4:185-191.

Antigen

ime

Antigen + adjuvant

Primary

immune

response

Adjuvanted vaccines can provide an improvedmagnitude, duration and cross-protection response

compared to unadjuvanted vaccines.


26/60

Description of immunity

Postinfection Postvaccine

Active Passive

Humoral Cellular

Antibacterial Antiviruses

Antitoxins Antifungal

Specific Nonspecific

Group specific, species specific Type-specific


27/60

The immune response• While many constituents of infectious

microorganisms and their products, such as

exotoxins, are or can be made to be

immunogenic, only a limited number

stimulate a protective immune response.

• The immune system is complex, and antigen

composition and presentation are critical forstimulation of the desired immune

responses.


28/60

The primary immune response• In the primary response to a vaccine antigen, an

apparent latent period of several days precedes

the detection of humoral and cell-mediated

immunity.

• Although the immune response begins withinitial recognition of the antigen by the immune

system, measurable circulating antibodies do

not appear for 7 to 10 days.


29/60

The primary immune response• The immunoglobulin class of the response also changes over time.

• The primary response is characterized by early-appearing IgM

antibodies.

• IgM antibodies generally exhibit only low affinity for the antigen,

whereas later appearing IgG antibodies display high affinity.

• Some individuals do not respond, even when presented repeatedly

with a vaccine antigen, often because they lack the major

histocompatibility complex determinants required to recognize the

antigen (primary vaccine failure) .


30/60

Primary immune response aftervaccination


31/60


32/60

The secondary immune response• Although levels of vaccine-induced antibodies may decline over time

(secondary vaccine failure ), revaccination or exposure to the

organism generally elicits a rapid protective secondary responseconsisting of IgG antibodies with little or no detectable IgM.

• This anamnestic response indicates that immunity has persisted.

• Lack of measurable antibody does not necessarily mean that the

individual is unprotected.

• The mere presence of detectable antibodies after the administrationof some vaccines and toxoids does not ensure clinical protection.

• A minimal circulating level of antibody is known to be required for

protection from some diseases (e.g., 0.01 IU/mL for tetanusantitoxin).


33/60


34/60

Mucosal immunity• Some pathogens are confined to and replicate only at mucosal

surfaces (e.g., Vibrio cholerae ), while others are able to penetrate the

mucosa and replicate (e.g., rubella virus, and influenza virus).

• At the mucosal site, these organisms induce secretory IgA.

• The induction of secretory IgA by vaccines may be an efficient way to

block the essential first steps in pathogenesis, whether the organism

is restricted to mucosal surfaces or invades the host across mucosal

surfaces.


35/60

Measurement of the immune response• Immune responses to vaccines are often measured

by the concentration of specific antibody in serum.

• While seroconversion serves as a dependable

indicator of an immune response, it measures only

one immunologic parameter and does notnecessarily indicate protection.

• The development of circulating antibodies after

immunization often correlates directly with clinical

protection (e.g., against rubella).


36/60

Herd immunity

• Vaccination provides direct protection against infection of

individuals, thereby decreasing the percentage of susceptible

persons within a population.

• At a definable prevalence of immunity in the population (herd

immunity ), an organism can no longer circulate freely among thesusceptible.

• This indirect protection of unvaccinated (nonimmune) persons is

called the herd immunity effect .


37/60

Herd immunity• The level of vaccination coverage needed to elicit a herd immunity effect

is dependent on the mixing patterns of the population and the biology of

the specific infectious agents. (e.g., measles viruses have high

transmission rates and therefore require a higher level of vaccine

coverage to elicit herd immunity than do organisms with lower

transmission rates, such as S. pneumoniae.)

• Herd immunity may wane if immunization programs are interrupted (as

was the case for diphtheria in the former Soviet Union) or if a sufficient

percentage of individuals refuse to be immunized (as occurred for

pertussis in the UK because concern about infrequent—albeit severe—

vaccine reactions came to exceed the fear of the disease itself).

• Loss of herd immunity led to renewed circulation of the organism and

subsequent large outbreaks.


38/60

Target populations and timing of

immunization• Different age groups have different disease attack rates, and

the effectiveness of vaccines depends on a variety of factors,

including the individual’s responsiveness to vaccines, the

demographic features of the populations at risk, and the

duration and character of the immunologic response.

• In vaccination programs schedules for immunization are based

on careful consideration of the variables affecting age-

dependent responses and population interactions (e.g., school

entry, college enrollment) as well as the feasibility of

implementation.


39/60


immunization• For common and highly communicable childhood diseases like

measles, the target population is the universe of susceptible

individuals, and the time to immunize is as early in life as isfeasible.

• Epidemiologic differences in measles transmission in different

settings dictate different strategies for immunization: – In the industrialized world, immunization with live-virus vaccine at 12

to 15 months of age has been the norm because the vaccine protects

95% of those immunized at this age and there is little measles

morbidity or mortality among very young infants. – In the developing world, measles is a significant cause of death in

young infants, and it is desirable to immunize children earlier to

narrow the window of vulnerability between the rapid decline of

maternal antibody after 4 to 6 months and the development ofvaccine-induced active immunity.


40/60


immunization

• Rubella is primarily a threat to the fetus; young infants and children

are not at risk of serious illness.

• An ideal strategy would be to immunize all women of reproductive age

before pregnancy.

• Because it is difficult to systematically vaccinate adolescent andyoung adult females and to assure the protection of as many women

as possible, rubella is included in a combination vaccine (MMR

vaccine) that is administered during infancy.


41/60


immunization

• Some vaccines were originally formulated primarily

for adults, e.g., influenza virus and polyvalentpneumococcal polysaccharide vaccines are used to

prevent pneumonia, hospitalizations, and deaths

among the elderly.• Infants can also be targeted to receive these adapted

for this age group vaccines.


42/60

Vaccine research

• Long, expensive, complicated process• On average,

– It has taken 10-15 years to develop a vaccine

– Costliness• Many experimental vaccines fail along the

way


43/60

Ideal vaccine should be

• Safe• Efficacious

• Available

• Affordable

• Stable


44/60

Strategy for vaccine development• Vaccine development depends on the systematic application of

a four-phase strategy:

– 1- studies in animals to identify protective antigens,

– 2- determination of how to present this antigen effectively to the

immune system,

– 3- assessment of the safety and immunogenicity of the preparationin small and then in large human populations at various ages,

– 4- evaluation of safety and efficacy in the target population.

• Each of these steps is simple in concept but difficult in

execution; failure at any level stops the process.


45/60

• The goal of vaccine development is not only to select the

correct antigens but also to ensure that the vaccines will result

in the type of immune response needed for protection, whether

T cell–mediated activation of macrophages or the generation of

cytotoxic T cells, B cell–mediated secretory IgA, or a particular

IgG subtype response to a specific polysaccharide epitope.• To create a deliverable vaccine, constituents other than

antigens are also required.

• These constituents can affect the immunogenicity, efficacy, and

safety of a vaccine and can render one formulation superior to

another.

Strategy of vaccine development

Constituents of vaccines


46/60

Constituents of vaccines

• Preservatives, stabilizers, antibiotics:

– these components are used to prevent deterioration of the vaccine

before use, to inhibit or prevent bacterial growth, or to stabilize the

vaccine; – any of these additions can cause allergic responses.

• Adjuvants:

– this type of additive (e.g., aluminum salts) is intended to enhance

the immune response (e.g., to toxoids).

• Suspending fluid:

– the suspending fluid can be sterile water, saline, buffer, or more

complex fluids derived from the growth medium or biologic systemin which the agent is produced (e.g., egg antigens, cell culture

ingredients, serum proteins).


47/60

Production of vaccines• As products to be given to healthy individuals to prevent disease,

vaccines must not only be efficacious but also cause no harm.

• Quality assurance is the responsibility of vaccine manufacturers.

• Proof of the safety, efficacy, sterility, and purity of products is

required before licensure, and sterility and purity are continually

monitored for all lots of vaccine after licensure.• Postmarketing studies of safety are part of routine regulatory

control.


48/60

Administration of vaccines

• Different vaccines should not be mixed in the same syringe unless

such a practice is specifically endorsed by licensure.

• The development and use of combinations of vaccines allows to

administer multiple injections at a single clinic visit.

• Without systematic attention to the completion of multiple-dosevaccine schedules, coverage rates for second, third, and booster

doses may drop off significantly.


49/60

Adverse events

• An adverse reaction or vaccine side effect is an untoward effect

caused by a vaccine that is extraneous to its primary purpose (to

produce immunity).

• An adverse event can be either a true vaccine reaction or a

coincidental event.

• Modern vaccines, while safe and effective, are associated withadverse events that range from infrequent and mild to rare and life-

threatening.

• The decision to recommend the use of a vaccine involves anassessment of the risks of disease and the benefits and risks of

vaccination.

Ad t


50/60

Adverse events

• Vaccine components, including protective antigens, animal proteins

introduced during vaccine production, and antibiotics or other

preservatives or stabilizers, can certainly cause allergic reactions in

some recipients.

• Allergic reactions may be local or systemic and include urticaria and

serious anaphylaxis.

• The most common extraneous allergen is egg protein introduced whenvaccines such as those for measles, mumps, influenza, and yellow

fever are prepared in embryonated eggs.

• Gelatin, which is used as a heat stabilizer, has been implicated in rare

but severe allergic reactions.

Contraindications


51/60

• Among the valid contraindications applicable to all vaccines are ahistory of anaphylaxis or other serious allergic reactions to a vaccine

or vaccine component and the presence of a moderate or severe

illness, with or without fever.

• Because of theoretical risks to the fetus, pregnant women should not

receive live vaccines.

• Live vaccines are contraindicated in immunocompromised persons.

• Diarrhea, minor respiratory illness (without fever), mild to moderate

local reactions to a previous dose of vaccine, the concurrent or recent

use of antimicrobial agents, mild to moderate malnutrition, and the

convalescent phase of an acute illness are not valid contraindicationsto routine immunization.

• Failure to vaccinate because of these conditions is viewed as a

missed opportunity for immunization.

Simultaneous Administration of Multiple Vaccines


52/60

Simultaneous Administration of Multiple Vaccines

• There are no contraindications to the simultaneous administration ofseveral vaccines.

• The use of combination vaccines can potentially reduce the required

number of injections from 9 to 3 during a child’s first 6 months of life

and from 21 to 13 during the first 2 years.

• Simultaneous administration of the most widely used live and

inactivated vaccines has not resulted in impaired antibody responses

or in increased rates of adverse reactions.

• Simultaneous administration is useful in any age group when the

potential exists for exposure to multiple infectious diseases during

travel to endemic countries.• When live-virus vaccines are not given together on the same day, an

interval of at least 30 days should be allowed.

Handling of vaccines


53/60

Handling of vaccines

• Vaccines must be handled and stored with

care.

• Vaccines should be kept at 2 to 8C and, with

the exception of varicella vaccine, should not

be frozen.

• Measles vaccine must be protected from

light, which inactivates the virus.


54/60

IMMUNOTHERAPYTreatment of the disease by Inducing, Enhancing or

Suppressing the Immune System.

Active Immunotherapy: -

It stimulates the body’s own

immune system to fight the

disease.

Passive Immunotherapy: -

It does not rely on the body to

attack the disease, instead

they use the immune system

components ( such as

antibodies) created outside the

body.


55/60

Passive immunity

• Passive immunity doesn’t last as long as

active immunity (only weeks or months).• No lymphocytes are stimulated to clone

themselves.

• No memory cells have been made.

• This type of immunity can only last as long

as the antibodies/antitoxins last in theblood.


56/60

Passive

immunotherapy

Injection

BoostersActiveimmunization

Time

Initialinoculation

A n t i b o d y ( I g G ,

I g M ) c o n c e n t r a t i o n ( t i t e r )

P i i i i


57/60

Passive immunization

• - is generally used to provide temporary immunity in

an unimmunized subject exposed to an infectious

disease when active immunization either is unavailableor has not been implemented before exposure (e.g., for

rabies).

• Passive immunization (immunotherapy) is used in the

treatment of certain disorders associated with toxins

(e.g., diphtheria, tetanus, botulism), in certain bites

(those of snakes and spiders), and as a specific or

nonspecific immunosuppressant [Rho(D) immune

globulin and antilymphocyte globulin, respectively].

Classification the serum


58/60

Classification the serum

preparations

• Homogeneous serum: serum obtainedfrom blood donor volunteers, have beenimmunized.

• Heterogeneous serum: serum obtainedfrom blood of animals hyperimmunized.

P i i i ti


59/60

Passive immunization

• Three types of preparations are used inpassive immunization:

– standard human immune serum globulin forgeneral use (e.g., globulin), administeredintramuscularly or intravenously;

– special immune serum globulins with a knowncontent of antibody to specific agents [e.g.,hepatitis B virus (HBV) or varicella-zoster immuneglobulin];

– animal sera and antitoxins.

P t i i ti


60/60

Postexposure immunization

• For certain infections, active or passive

immunization soon after exposure preventsor attenuates disease expression.

• Recommended postexposure immunization

regimens against tetanus, rabies.

5.14 immunoprophylaxis immunotherapy

Documents