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IMMUNIZATION - INTRODUCTION
Vaccination vs immunization
• ‘Vaccination’ is a process of inoculating the
vaccine/antigen in to the body.
• The vaccinee may or may not seroconvert
• The process of inducing immune response,
which can be ‘humoral’ or ‘cell-mediated’ in
the vaccinee is called ‘immunization’.
Active vs passive immunization
Innate vs adaptive immunity
Humoral vs cell mediated immunity
• Vaccines confer protection against diseases by
inducing both antibodies and T-cells.
• Antibodies are of several different types (IgG,
IgM, IgA, IgD and IgE) and they differ in their
structure, half life, site of action and mechanism
of action.
• Humoral immunity is the principal defence
mechanism against extracellular microbes and
their toxins.
• B lymphocytes secrete antibodies that act by
neutralization, complement activation or by
promoting opsono- phagocytosis.
• Cell mediated immunity (CMI) is the principal
defence mechanism against intracellular
microbes.
• The effectors of CMI, the T cells are of two
types.
• The helper T cells secrete cytokines that
stimulate the proliferation and differentiation
of T cells as well as other cells including B
lymphocytes, macrophages and NK cells.
• The cytotoxic T cells act by lysing infected
cells.
VACCINES
• Live vaccines are attenuated (modified) live
organisms, which have immunogenicity i.e. can
generate antibodies, but have lost pathogenicity
i.e. capability to cause disease.
• Efficiently trigger the activation of both innate
and adaptive immune system.
• Toll-like receptors (TLRs) - single membrane-
spanning non-catalytic receptors that recognize
structurally conserved molecules derived from
microbes.
• Pattern is very similar to natural infection
Inactivated vaccines may consist of
• whole inactivated organisms like whole cell
pertussis, typhoid, rabies, inactivated polio
• modified exotoxins called ‘toxoids’ like diphtheria
toxoid or tetanus toxoid
• subunits like polysaccharide antigens of
salmonella typhi, Hemophilus influenzae type-B
(Hib), and surface proteins of hepatitis B
Conjugation of the polysaccharide with a protein
carrier significantly improves the immune
response
T CELL DEPENDENCY
• Protein antigens stimulate both B and T cells, while
polysaccharides stimulate only B cells.
• Accordingly called T cell dependent and independent
antigens
• Proteins or conjugated polysaccharide – taken up by
APC, activate follicular dendritic cells (FDC) present in
germinal centre. Required for massive clonal
proliferation, class switch in immunoglobulins, affinity
maturation.
• Results in plasma cells that deposit in niches of bome
marrow and provide long lasting immunity.
• Generation of memory B cells – follow rapid kinetics
during second exposure
• Polysaccharide vaccines – fail to recruit helper T
cells. Results in plasma cells that persists till
dissolution of germinal centres. Decline in
antibody levels after dissolution of GC.
• Subsequent exposure – same kinetics
• Hyporesponsiveness - revaccination with PS may
indude lower Ab responses. Esp seen with
menigococci and pneumococci. Hence
recommended only single booster even for
lifelong immunity.
• PS are unable to evoke response in < 2 yrs –
immaturity of marginal zone.
Vaccination schedules
• Interval b/w doses 0-1-6 more immunogenic.
• Interval b/w primary doses – 4 weeks
• Interval b/w primary and booster – min 4
months
• Young age immunization problems – maternal
antibodies and immature immune system.
• Strategies followed –
1. Increased no. of vaccine doses
2. Adjuvants
3. Boosters at later age
• Early, accelerated schedules are practiced in
developing countries
• Adjuvants: Adjuvants are potentiating agents
and immunostimulants.
• Simultaneous administration of adjuvant –
potentiate immune response both humoral and
CMI.
Classic – mineral oil suspension, alluminium
salts
Newly developed – liposomes, immune
stimulating complex, squalene complex,
bordetella, vit A, beryllium salts, toxic salts of
silica.
• Direct increase in number of cells which
involved in antibody production.
• Ensuring effective processing of antibody.
• Prolonging the duration of antigen
• Increasing the synthesis and release of
antibody from antibody forming cells.
• Rationale for Hep B/ BCG/ OPV @ birth
Although maternal antibodies interfere with the
induction of infant antibody responses, they
may allow a certain degree of priming, i.e. of
induction of memory B cells – hence Hep B
Maternal Abs don’t interfere with T cell
responses – hence BCG. Sometimes enhance
also.
No maternal IgA in the gut to neutralize the
virus – hence OPV
BASIC TERMINOLOGIES
• Basic reproductive no.(Ro) – measures avg no.
of secondary cases generated by 1 primary
case in a susceptible population.
Ro < 1 , disease is declining (herd effect)
Ro > 1 , outbreak is occuring
• Immunogenecity – ability of vaccine to induce
antibodies.
• Vaccine efficacy – ability to protect an
individual. Assessed by clinical trials, cohort
studies or case control studies.
VE = ARU – ARV * 100
ARU
• Vaccine effectiveness – ability to protect
community. Sum of vaccine efficacy and herd
effect. Revealed after vaccine is introduced
into program.
• Herd immunity – denotes resistance of a
population to the spread of vaccine preventable
diseases where causative organisms spread from
human to human.
• Proportion immune in a herd
• Herd effect –protection offered to unvaccinated
members when good proportion (usually more
than 85%) of the herd is vaccinated.
• Due to reduced carriage of the causative
microorganism by the vaccinated cohort and thus
is seen only with vaccines against those diseases
where humans are the only source
• Contact immunity – vaccinated individual can
pass on vaccine to another individual
• Unique property of some vaccines
• Herd immunity vs contact immunity
• Virtually by breaking the transmission of the
infection or lessening the chances of
susceptible individuals coming in contact with
infective individual.
• Clinical practice - contact immunity does not
play significant role, while herd protection
plays a major role
General recommendations
• Ideal immunization schedule
epidemiologicaly relevant,
immunologicaly competent,
technologicaly feasible,
socially acceptable,
affordable and sustainable
• Number of doses
Live vaccines induce immunity with a single
dose; inactivated vaccines require multiple
doses (initial doses to prime and later doses to
boost)
Multiple doses of OPV – reduced take up of virus
• Vaccination schedules in developing
countries:
6, 10, 14 weeks e.g. India, Kenya, Madagascar,
Mozambique, Philippines,
2, 4, 6 months e.g. Egypt, Chile, Mexico,
Thailand, Uruguay, Argentina, Brazil
2, 3, 4 months e.g. Gambia, Indonesia, Turkey,
Vietnam
2, 3, 5 months e.g. Malaysia
3, 4, 5 months e.g. China
• age of administration of vaccines
Nature of the vaccine- killed, live,
polysaccharide
Age and immune status of the recipient i.e
ability of persons of a certain age to respond
to the vaccine and potential interference with
the immune response by passively transferred
maternal antibody or previously administered
antibody containing blood products.
Age-specific risks for disease, age specific risks
for complications.
• IAPCOI has categorized vaccines into four categories:
Vaccines covered under Expanded Program on Immunization
(EPI):
BCG, OPV, DTwP, Measles, DT, TT, Hep B, MMR, Hib
Vaccines recommended by IAP in addition to EPI vaccines:
Typhoid, IPV, Tdap, Td, HPV
Vaccines which are to be given after one-to-one discussion with
the parents: Hepatitis A, PCV13, Chicken Pox, DTaP, Rotavirus
Vaccines to be given in special circumstances:
Rabies, Influenza, PPV23, Japanese encephalitis,
Meningococcal.
Practice of vaccination
• Safe injection practices
Hands should be washed with soap and water or
cleaned with an alcohol based hand rub
Skin at the injection site should be prepared with
70% isopropyl alcohol or another disinfecting
agent and allowed to dry before injection.
Separate disposable syringes and needles should be
used for each injection.
Pre-filling of syringe should be avoided as most
vaccines appear similar and administration error
can occur.
• Instructions for injectables
To prevent accidental needle-sticks or reuse, a needle
should not be recapped after use.
Disposable needles and syringes should be discarded
promptly in puncture-proof, labeled containers.
Changing needles between drawing vaccine into the
syringe and injecting it into the child is not necessary.
Different vaccines should not be mixed in the same
syringe unless specifically licensed and labeled for such
use.
Whenever possible, patients should be observed for an
allergic reaction for 15 to 20 minutes after receiving
immunization.
• Instructions for oral
Vaccine must be swallowed and retained. OPV
should be repeated immediately if a child spits it
out, fails to swallow, or regurgitates a dose within
10 minutes after administration.
If the second dose is not retained, neither dose
should be counted, and vaccine should be re-
administered.
Breastfeeding does not interfere with successful
immunization with oral vaccines (e.g., OPV,
Rotavirus).
Regarding rotavirus vaccines, instructions given by
the manufacturer should be followed if the child
spits out the vaccine.
• Site and route of administration
Preferred site is anterolateral aspect of upper
thigh or deltoid area of upper arm
Upper outer quadrant of buttocks not
recommended
Distance separating the 2 injections is arbitrary
but should be at least 1 inch so that local
reactions are unlikely to overlap
“Aspiration” by gently pulling back – no
recommendations
Other recommendations
• Vaccines which contain stabiliser and
preservative generally cause local reaction like
pain and swelling. Hence administered IM
• All injections meant for SC can be safely given IM
not vice versa
• Antibody-containing products and inactivated
antigen can be administered simultaneously at
different sites or at any time interval between
doses. Non simultaneous administration can also
be done at any interval.
• Antibody containing products and live antigen
should not be administered simultaneously.
Antibody containing products can be
administered after 2 weeks of live antigen
without any interference with seroconversion.
• Measles and varicella containing vaccines
should be administered 3-6 months after
immunoglobulins or blood transfusion
• Vaccines in bleeding disorders – Unless
contraindicated, subcutaneous route should
be used. For those vaccines (aluminium
adjuvanted) which need to be given only IM,
vaccination should be planned after factor
replacement.
• Tuberculin skin test – same visit during which
live viral vaccines, such as MMR, Measles,
Varicella
• Otherwise Tuberculin testing should be
postponed for 4 to 6 weeks
Contraindications and Precautions
• Contraindication – condition in recipient
increases chances of serious adverse reaction
Severe anaphylaxis, acute encephalopathy, SCID
Temporary – pregnancy, immunosuppression
Vaccines should not be administered.
• Precaution – condition in recipient increases
chances of adverse reaction or might
compromise ability to induce immunity.
High grade fever, persistent cry, seizures within 3
days.
Vaccines should be deferred.
REFERENCES
• Immunization in clinical practice – Naveen
Thaker
• Partha’s immunization digest
• FAQ on immunization practices – Vipin
Vashistha
Basic terminologies vaccines

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Basic terminologies vaccines

  • 2. Vaccination vs immunization • ‘Vaccination’ is a process of inoculating the vaccine/antigen in to the body. • The vaccinee may or may not seroconvert • The process of inducing immune response, which can be ‘humoral’ or ‘cell-mediated’ in the vaccinee is called ‘immunization’.
  • 3. Active vs passive immunization
  • 4.
  • 6.
  • 7. Humoral vs cell mediated immunity • Vaccines confer protection against diseases by inducing both antibodies and T-cells. • Antibodies are of several different types (IgG, IgM, IgA, IgD and IgE) and they differ in their structure, half life, site of action and mechanism of action. • Humoral immunity is the principal defence mechanism against extracellular microbes and their toxins. • B lymphocytes secrete antibodies that act by neutralization, complement activation or by promoting opsono- phagocytosis.
  • 8.
  • 9. • Cell mediated immunity (CMI) is the principal defence mechanism against intracellular microbes. • The effectors of CMI, the T cells are of two types. • The helper T cells secrete cytokines that stimulate the proliferation and differentiation of T cells as well as other cells including B lymphocytes, macrophages and NK cells. • The cytotoxic T cells act by lysing infected cells.
  • 10.
  • 11. VACCINES • Live vaccines are attenuated (modified) live organisms, which have immunogenicity i.e. can generate antibodies, but have lost pathogenicity i.e. capability to cause disease. • Efficiently trigger the activation of both innate and adaptive immune system. • Toll-like receptors (TLRs) - single membrane- spanning non-catalytic receptors that recognize structurally conserved molecules derived from microbes. • Pattern is very similar to natural infection
  • 12. Inactivated vaccines may consist of • whole inactivated organisms like whole cell pertussis, typhoid, rabies, inactivated polio • modified exotoxins called ‘toxoids’ like diphtheria toxoid or tetanus toxoid • subunits like polysaccharide antigens of salmonella typhi, Hemophilus influenzae type-B (Hib), and surface proteins of hepatitis B Conjugation of the polysaccharide with a protein carrier significantly improves the immune response
  • 13. T CELL DEPENDENCY • Protein antigens stimulate both B and T cells, while polysaccharides stimulate only B cells. • Accordingly called T cell dependent and independent antigens • Proteins or conjugated polysaccharide – taken up by APC, activate follicular dendritic cells (FDC) present in germinal centre. Required for massive clonal proliferation, class switch in immunoglobulins, affinity maturation. • Results in plasma cells that deposit in niches of bome marrow and provide long lasting immunity. • Generation of memory B cells – follow rapid kinetics during second exposure
  • 14. • Polysaccharide vaccines – fail to recruit helper T cells. Results in plasma cells that persists till dissolution of germinal centres. Decline in antibody levels after dissolution of GC. • Subsequent exposure – same kinetics • Hyporesponsiveness - revaccination with PS may indude lower Ab responses. Esp seen with menigococci and pneumococci. Hence recommended only single booster even for lifelong immunity. • PS are unable to evoke response in < 2 yrs – immaturity of marginal zone.
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  • 17. Vaccination schedules • Interval b/w doses 0-1-6 more immunogenic. • Interval b/w primary doses – 4 weeks • Interval b/w primary and booster – min 4 months
  • 18. • Young age immunization problems – maternal antibodies and immature immune system. • Strategies followed – 1. Increased no. of vaccine doses 2. Adjuvants 3. Boosters at later age • Early, accelerated schedules are practiced in developing countries
  • 19. • Adjuvants: Adjuvants are potentiating agents and immunostimulants. • Simultaneous administration of adjuvant – potentiate immune response both humoral and CMI. Classic – mineral oil suspension, alluminium salts Newly developed – liposomes, immune stimulating complex, squalene complex, bordetella, vit A, beryllium salts, toxic salts of silica.
  • 20. • Direct increase in number of cells which involved in antibody production. • Ensuring effective processing of antibody. • Prolonging the duration of antigen • Increasing the synthesis and release of antibody from antibody forming cells.
  • 21. • Rationale for Hep B/ BCG/ OPV @ birth Although maternal antibodies interfere with the induction of infant antibody responses, they may allow a certain degree of priming, i.e. of induction of memory B cells – hence Hep B Maternal Abs don’t interfere with T cell responses – hence BCG. Sometimes enhance also. No maternal IgA in the gut to neutralize the virus – hence OPV
  • 22. BASIC TERMINOLOGIES • Basic reproductive no.(Ro) – measures avg no. of secondary cases generated by 1 primary case in a susceptible population. Ro < 1 , disease is declining (herd effect) Ro > 1 , outbreak is occuring • Immunogenecity – ability of vaccine to induce antibodies.
  • 23. • Vaccine efficacy – ability to protect an individual. Assessed by clinical trials, cohort studies or case control studies. VE = ARU – ARV * 100 ARU • Vaccine effectiveness – ability to protect community. Sum of vaccine efficacy and herd effect. Revealed after vaccine is introduced into program.
  • 24. • Herd immunity – denotes resistance of a population to the spread of vaccine preventable diseases where causative organisms spread from human to human. • Proportion immune in a herd • Herd effect –protection offered to unvaccinated members when good proportion (usually more than 85%) of the herd is vaccinated. • Due to reduced carriage of the causative microorganism by the vaccinated cohort and thus is seen only with vaccines against those diseases where humans are the only source
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  • 26. • Contact immunity – vaccinated individual can pass on vaccine to another individual • Unique property of some vaccines • Herd immunity vs contact immunity • Virtually by breaking the transmission of the infection or lessening the chances of susceptible individuals coming in contact with infective individual. • Clinical practice - contact immunity does not play significant role, while herd protection plays a major role
  • 27. General recommendations • Ideal immunization schedule epidemiologicaly relevant, immunologicaly competent, technologicaly feasible, socially acceptable, affordable and sustainable
  • 28. • Number of doses Live vaccines induce immunity with a single dose; inactivated vaccines require multiple doses (initial doses to prime and later doses to boost) Multiple doses of OPV – reduced take up of virus
  • 29. • Vaccination schedules in developing countries: 6, 10, 14 weeks e.g. India, Kenya, Madagascar, Mozambique, Philippines, 2, 4, 6 months e.g. Egypt, Chile, Mexico, Thailand, Uruguay, Argentina, Brazil 2, 3, 4 months e.g. Gambia, Indonesia, Turkey, Vietnam 2, 3, 5 months e.g. Malaysia 3, 4, 5 months e.g. China
  • 30. • age of administration of vaccines Nature of the vaccine- killed, live, polysaccharide Age and immune status of the recipient i.e ability of persons of a certain age to respond to the vaccine and potential interference with the immune response by passively transferred maternal antibody or previously administered antibody containing blood products. Age-specific risks for disease, age specific risks for complications.
  • 31. • IAPCOI has categorized vaccines into four categories: Vaccines covered under Expanded Program on Immunization (EPI): BCG, OPV, DTwP, Measles, DT, TT, Hep B, MMR, Hib Vaccines recommended by IAP in addition to EPI vaccines: Typhoid, IPV, Tdap, Td, HPV Vaccines which are to be given after one-to-one discussion with the parents: Hepatitis A, PCV13, Chicken Pox, DTaP, Rotavirus Vaccines to be given in special circumstances: Rabies, Influenza, PPV23, Japanese encephalitis, Meningococcal.
  • 32. Practice of vaccination • Safe injection practices Hands should be washed with soap and water or cleaned with an alcohol based hand rub Skin at the injection site should be prepared with 70% isopropyl alcohol or another disinfecting agent and allowed to dry before injection. Separate disposable syringes and needles should be used for each injection. Pre-filling of syringe should be avoided as most vaccines appear similar and administration error can occur.
  • 33. • Instructions for injectables To prevent accidental needle-sticks or reuse, a needle should not be recapped after use. Disposable needles and syringes should be discarded promptly in puncture-proof, labeled containers. Changing needles between drawing vaccine into the syringe and injecting it into the child is not necessary. Different vaccines should not be mixed in the same syringe unless specifically licensed and labeled for such use. Whenever possible, patients should be observed for an allergic reaction for 15 to 20 minutes after receiving immunization.
  • 34. • Instructions for oral Vaccine must be swallowed and retained. OPV should be repeated immediately if a child spits it out, fails to swallow, or regurgitates a dose within 10 minutes after administration. If the second dose is not retained, neither dose should be counted, and vaccine should be re- administered. Breastfeeding does not interfere with successful immunization with oral vaccines (e.g., OPV, Rotavirus). Regarding rotavirus vaccines, instructions given by the manufacturer should be followed if the child spits out the vaccine.
  • 35. • Site and route of administration Preferred site is anterolateral aspect of upper thigh or deltoid area of upper arm Upper outer quadrant of buttocks not recommended Distance separating the 2 injections is arbitrary but should be at least 1 inch so that local reactions are unlikely to overlap “Aspiration” by gently pulling back – no recommendations
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  • 39. Other recommendations • Vaccines which contain stabiliser and preservative generally cause local reaction like pain and swelling. Hence administered IM • All injections meant for SC can be safely given IM not vice versa • Antibody-containing products and inactivated antigen can be administered simultaneously at different sites or at any time interval between doses. Non simultaneous administration can also be done at any interval.
  • 40. • Antibody containing products and live antigen should not be administered simultaneously. Antibody containing products can be administered after 2 weeks of live antigen without any interference with seroconversion. • Measles and varicella containing vaccines should be administered 3-6 months after immunoglobulins or blood transfusion
  • 41. • Vaccines in bleeding disorders – Unless contraindicated, subcutaneous route should be used. For those vaccines (aluminium adjuvanted) which need to be given only IM, vaccination should be planned after factor replacement. • Tuberculin skin test – same visit during which live viral vaccines, such as MMR, Measles, Varicella • Otherwise Tuberculin testing should be postponed for 4 to 6 weeks
  • 42. Contraindications and Precautions • Contraindication – condition in recipient increases chances of serious adverse reaction Severe anaphylaxis, acute encephalopathy, SCID Temporary – pregnancy, immunosuppression Vaccines should not be administered.
  • 43. • Precaution – condition in recipient increases chances of adverse reaction or might compromise ability to induce immunity. High grade fever, persistent cry, seizures within 3 days. Vaccines should be deferred.
  • 44. REFERENCES • Immunization in clinical practice – Naveen Thaker • Partha’s immunization digest • FAQ on immunization practices – Vipin Vashistha