Immunization (Part

One)
Dr. Mukesh Bhatta
Immunity
• Immunity is referred to as the resistance exhibited by the host
towards injury caused by microorganisms and their products.

• It is classified as
• Innate immunity(Native)

• Acquired immunity(Adaptive)
 Innate immunity Adaptive immunity

IMMUNOLOGY OF VACCINATION
Its response is antigen independent ; immediate response . Its response is antigen dependent ; lag time between exposure and
maximal response

It is not antigen specific; Exposure does not result in induction of antigen specific; Exposure results in induction of memory cells
memory cells

Some of its cellular components or their products may aid specific Some of its products may aid specific immunity
immunity

triggers development of adaptive immunity

Vaccines that stimulate innate immunity effectively are better

immunogens. This can be achieved by live vaccines, adjuvants, toll-
like receptor (TLR) agonists, live vectors, and deoxyribonucleic acid
(DNA) vaccines.
Difference between active and
passive immunity
Active immunity Passive immunity
Produce actively by hosts immune system Received passively, no active participation
of hosts immune system
Induced by infections or by immunogens Conferred by administration of ready made
antibodies
Long-lasting and effective protection Short term and effective protection
Immunity effective only after lag Immediate immunity
period( time required for generation of
antibodies)
Immunological memory present No memory
Booster effect on subsequent dose Subsequent dose less effective
Not applicable in immunodeficient Applicable in immunodeficient
 Basic immunology
Antigen

Antigen presenting cells

T- Helper lymphocytes

Th- 1 Memory cell Th-2

Cytotoxic T cells Memory Cells B - Cells

CMI Memory Antibody

Principle of Immunization
• When exposed to a pathogenic organism, the body
mounts an immune response.

• When exposed to an infectious agent the

second time, the host immune response is
fairly rapid and sufficient to prevent the
disease.
Vaccination and Immunization
definitions…

Vaccine : a suspension of live (usually attenuated)

or inactivated microorganisms (eg bacteria or
viruses) or fractions thereof administered to induce
immunity and prevent infectious disease or its
sequels.
Vaccination and Immunization
definitions…

• Vaccination (vacca=cow): physical act of administering any vaccine

or toxoid

• Immunization : process of inducing or providing immunity by

administering an immunobiological.

• Immunization can be active or passive.

Sero conversion and sero protection
Sero conversion:
• Change from antibody negative state to antibody positive state.
Sero protection:
• The state of protection (from disease) due to presence of humoral
immunity.
Live vaccines
• Live vaccines are made from live infectious agents without any
amendment.

• The only live vaccine is variola small pox vaccine, made of live vaccinia
cow-pox virus (not variola virus) which is not pathogenic but
antigenic, giving cross immunity for variola.
Live attenuated(avirulent)vaccines
• Virulent pathogenic organisms are treated to become attenuated and avirulent but
antigenic. They have lost their capacity to induce full-blown disease but retain their
immunogenicity
• BCG ,typhoid oral, plague, oral polio, yellow fever, measles , mumps, rubella, intranasal
influenza, typhus.
• Live attenuated vaccines shouldn’t be administered to persons with suppressed
immune response eg
Leukemia and lymphoma
Other malignancies
Receiving corticosteroids and anti-metabolic agents
Radiation
Pregnancy
Inactivated (killed) vaccines
• Organisms are killed or inactivated by heat or chemicals but remain
antigenic. They are usually safe but less effective than live attenuated
vaccines. The only absolute contraindication to their administration is
a severe local or general reaction to a previous dose.

• Eg typhoid, cholera, pertusis, plague , rabies, salk polio , intramuscular

influenza, japanese encephalitis
Toxoids
• They are prepared by detoxifying the exotoxins of some bacteria
which render them antigenic but not pathogenic. Adjuvant ( eg alum
precipitation) is used to increase the potency of vaccine.
• The antibodies produces in the body as a consequence of toxoid
administration neutralize the toxic moiety produced during infection
rather than act upon the organism itself. In general toxoids are highly
efficacious and safe immunizing agents.
• Eg diphtheria, tetanus
Polysaccharide and
polypeptide(cellular fraction) vaccine
• Prepared from extracted cellular fractions eg meningoccocal vaccine
from the polysaccharide antigen of the cell wall, the pneumoccocal
vaccine from the polysaccharide contain in the capsule of the
organism, and hepatitis B polypeptide vaccine.
• High efficacy and safety.
• Subunit vaccines comprising only of the polysaccharide (PS) antigens
are called unconjugated vaccines.
• Conjugation of the PS with a protein carrier (glycoconjugates)
significantly improves the immune response
Surface antigen( recombinant)
vaccines
• It is prepared by recombinant DNA technology. This involves inserting
the DNA encoding an antigen that stimulates an immune response .

• Eg cloning HBsAg gene in yeast cells where it is expressed. HBsAg

produced is then used for vaccine preparations.

• Their efficacy and safety also appear to be high

Types of Vaccines
• Live attenuated
• Inactivated/Killed
• Killed organism: Whole cell pertusis
• Toxoid/toxins (Diphtheria, tetanus)
• Polysaccharide antigen
• Subunit : Hib, Hep A, B, typhoid, meningococcal, influenza
• Nucleic acid ( DNA,RNA)
Types of Vaccines:
Type of Antigen Examples
Live bacteria, attenuated BCG, Ty 21a
Live virus, attenuated OPV,MMR, JE ,Varicella, Rota
Killed bacteria Pertussis, Typhoid,Cholera
Killed virus IPV, Rabies, HAV ,IIV
Toxoid DT, TT, Td
Capsular polysaccharide Ty Vi, Hib, meningococcal,
pneumococcal
Viral subunit Hepatitis B, HPV
Bacterial subunit Acellular pertussis
Immune response to vaccination: Primary response

• Observed after the first injection

• Has three distinct periods
• Latency period: Time between vaccine injection and appearance of
the serum antibodies; Ranges from 24 hours to 2 weeks.
• Growth period: Following latency period, antibodies increase
exponentially within a lapse of time varying from 4 days to 4 weeks.
Usually 3 wks for tetanus or diphtheria toxoids; 2 wks for microbial
vaccines. Igm produced earlier.
• Period of decline: After reaching a maximum, the Ab level declines
rapidly at first, and then slowly. IgA and IgM decline rapidly than IgG
Immune response to vaccination:
Secondary response
• Induced by reintroduction of the same antigen after a suitable period of time

• Rapid and large number of ab secreted esp IgG.

• The growth phase remains exponential; but its development is more rapid, whereas
the period of decline is longer.
• If the second injection is given before the complete disappearance of the antibodies
induced by the first injection, there is a temporary decrease in the antibody level,
because of the elimination of the antigens by the preformed antibodies.
• The secondary antibodies persist for a longer period of time, and sometimes
indefinitely.
• Memory cells play role.
Maternal antibodies and immune
response
• IgG transplacentaly transferred (antiviral and antibacterial)
• Persist for 5-9 months
• Hence timing of vaccination crucial, esp in case of live attenuated
vaccines (measles, mumps or rubella)
Herd immunity and Herd Effect
• Herd Immunity is the proportion of immune individuals in a population.
• Immunity may have come through natural disease or through
immunization.
• Herd effect is the protection offered to unvaccinated members when
good proportion (usually more than 85%) of the population is vaccinated.
• Herd effect is d/t reduced carriage of the causative microorg by the
vaccinated cohort and thus is seen only with vaccines against those
diseases where humans are the only source
• Tetanus: no herd effect
Vaccine immunogenicity, efficacy
and effectiveness
• Vaccine immunogenicity is the ability of a vaccine to induce antibodies
which may or may not be protective. The protective threshold for most
vaccines is defined.
• Vaccine efficacy (VE) is the ability of the vaccine to protect an individual
under experimental conditions. It can be assessed through clinical trials,
cohort studies or case control studies.
• VE=disease in unvaccinated-dis in vaccinated/dis in unvaccinated
• Vaccine effectiveness is the ability of a vaccine to protect the community
under programmatic conditions.
• Vaccine effectiveness is the combination of vaccine efficacy, coverage and
herd effect.
Level of effectiveness
• Absolute protective(100%): yellow fever vaccine
• All most absolutely protective(99%): varriola, measles mumps rubella,
diphtheria and tetanus toxoids
• Highly protective(80-95%): polio, BCG, hepatitis B and pertusis
vaccine
• Moderately protective(40-60%): TAB, cholera vaccine, and influenza
killed vaccine
INJECTION PROCEDURE

• Sterile Technique and Injection Safety

• A separate needle and syringe should be used for each injection. Changing
needles between drawing vaccine from a vial and injecting it into a
recipient is not necessary.

• Different vaccines should never be mixed in the same syringe unless

specifically licensed for
• Prefilling of syringes should not be done
Salient points regarding vaccination

• Generally, there is no harm done if SC vaccines are given IM.

• However, IM vaccines not to be given Subcutaneously due to risk of
side effects (as seen with aluminum adjuvanted vaccines) or reduced
efficacy (due to reduced blood supply in SC tissue and hence reduced
immunogenicity).
• The gluteal region should never be used for IM d/t risk of sciatic nerve
injury and reduced efficacy (rabies and hepatitis B vaccines).
Salient points regarding vaccination
• When used at the recommended sites where no large blood vessels
exist, pulling back of the syringe to check for blood is not
recommended.
• The needle should be withdrawn a few seconds after finishing
administration of the vaccine (to prevent backflow of vaccine into the
needle track) following which the injection site should be pressed
firmly for a few seconds with dry cotton.
• The injection site should not be rubbed following injection.
Salient points regarding vaccination

• Vaccination at birth means as early as possible within 24–72 hours after birth or at
least not later than 1 week after birth
• Whenever multiple vaccinations are to be given simultaneously, they should be given
within 24 hours if simultaneous administration is not feasible due to some reasons
• The recommended age in weeks/months/years means completed weeks/
months/years
• Any dose not administered at the recommended age should be administered at a
subsequent visit, when indicated and feasible
• The use of a combination vaccine generally is preferred over separate injections of its
equivalent component vaccines
Salient points regarding vaccination
• When two or more live parenteral/intranasal vaccines are not administered
on the same day, they should be given at least 28 days (4 weeks) apart; this
rule does not apply to live oral vaccines
• If given <4 weeks apart, the vaccine given second should be repeated
• The minimum interval between 2 doses of inactivated vaccines is usually 4
weeks (exception rabies)
• Vaccine doses administered up to 4 days before the minimum interval or age
can be counted as valid (exception rabies).
• If the vaccine is administered >5 days before minimum period, it is counted
as invalid dose
Principles in administration of vaccines
Combination Recommendation
≥ 2 killed antigens Give simultaneously or at any interval

Killed and live antigens Can be given simultaneously or at any

interval.
≥ 2 live antigens 4 weeks minimum interval if not given
together, except OPV and BCG.
IG and corresponding For MMR : 3 mo -11 months
antigen For Hep B, tetanus, Rabies – can be given
simultaneously
Salient points regarding vaccination
• Any number of antigens can be given on the same day
• 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
• Observe for an allergic reaction (anaphylaxis) for 15–20 minutes after
receiving immunization(s)
• When necessary, two vaccines can be given in the same limb (1–2
inches apart) at a single visit
Salient points regarding vaccination
• The anterolateral aspect of the thigh is the preferred site for two
simultaneous intramuscular (IM) injections because of its greater
muscle mass
• The distance separating the two injections is arbitrary but should be
at least 1 inch so that local reactions are unlikely to overlap
• A previous immunization with a dose that was less than the standard
dose or one administered by a nonstandard route should not be
counted, and the person should be re-immunized as appropriate for
age
Salient points regarding vaccination

• If multiple vaccines are administered at a single visit, administration

of each preparation at a different anatomic site is desirable.
• For infants and younger children, if more than two vaccines must be
injected in a single limb, the thigh is the preferred site because of the
greater muscle mass; the injections should be sufficiently separated
(i.e. 1 inch or more if possible) so that any local reactions can be
differentiated.
• For older children and adults, the deltoid muscle can be used for
more than one IM injection
Salient points regarding vaccination
• If a vaccine and an immune globulin preparation are administered
simultaneously [e.g. Td/ Tdap and tetanus immune globulin (TIg),
hepatitis B and hepatitis B immunoglobulin (HBIg)], separate
anatomic sites should be used for each injection. The location of each
injection should be documented in the patients’ medical record
Subcutaneous injection
AGE SITE TYPE OF NEEDLE COMMENTS
INFANTS Thigh 22-25 gauge; 5/8 inch For subcutaneous
injection, needle should
enter at 45 degree to the
skin
>12 MONTHS Outer triceps 22-25 gauge; 5/8 inch
Intradermal injection
AGE SITE TYPE OF NEEDLE COMMENTS
All ages Left deltoid 26-27 gauge; 0.5 inch A 5 mm wheal should be
raised
Site and needle length by age for IM
Age Group Needle length, Injection site
inches(mm)
Newborn(Preterm & 5/8(16)
Term) and < 1 month (22 to 25 gauge needle) Anterolateral thigh muscle

1 mo -12 month 1(25) Anterolateral thigh muscle

5/8 - 1 (16-25) Deltoid muscle

Toddlers and children 1—11/4 (25-32) Anterolateral thigh muscle

Adolescence & adult

< 90 kg 1(25) Deltoid muscle
> 90 kg 11/2(38) Deltoid muscle
 Managing Injection pain
• Oral vaccines generally should be administered prior to
administering injection
• child should be held on the lap of a parent; not be
placed supine position
• Rubbing or stroking the skin near the injection site
• Age appropriate distraction
• Reassurance and apologies may increase distress and
pain.
• Pretreatment (30–60 minutes before injection) with 5% topical
lidocaine-prilocaine emulsion
• Topical lidocaine-prilocaine emulsion should not be used on infants
aged <12 months who are receiving treatment with methemoglobin-
inducing agents because of the possible development of
methemoglobinemia

• Acetaminophen may be used immediately following DTP vaccination

at the rate of 15 mg/kg/dose to reduce the discomfort and fever
 Vaccine Dose(s) Age of Route of
administration administration/site
BCG (Bacillus- Calmette Guerin)i.e 1 (0.05 ml) At birth Intradermal (I.D)/Right upper
Copenhagen strain. arm
Pentavalent i.e DPT-Hep B-HiB 3 (0.5 ml) 6 , 10 , 14 wks Intramuscular(I.M)/ left
(Diphtheria , pertussis, tetanus , anterolateral thigh
Hepatitis B , Hemophilus influenza

OPV (Oral Polio vaccine) 3 ( 2 drops) 6, 10 , 14 wks Oral

Rotavirus Vaccine (Rotarix G1,P8) 2 ( 1.5 ml) 6 , 10 wks Oral/ given between cheek
and gum
PCV-10 ( Pneumococcal conjugate 3 (0.5 ml ) 6 , 10 wks and 9 months Intramuscular (I.M)/Right
vaccine ) anterolateral thigh

fIPV (fractional inactivated polio vaccine 2( 0.1 ml) 6, 14 wks Intradermal (I.D)/left upper
) arm
MR (measles ,Rubella) 2( 0.5 ml) 9 and 15 months Subcutaneous (S.C)/left upper
arm
JE (Japanese encephalitis) i.e SA 14-14- 1 (0.5 ml ) 12 -23months Subcutaneous ( S.C)/ right
2 strain upper and outer thigh

Td (Tetanus diphtheria) 2 (0.5 ml ) pregnancy, 2 doses 1 month Intramuscular (I.M)/left upper

apart arm
Contraindications for vaccination
• History of anaphylaxis to a previous dose or to a vaccine
component.
• Live vaccines in severely immunocompromised or in whom immune
function is uncertain.
• Children who experienced encephalopathy within 7 days after
administration of a previous dose of DTwP , DTaP or Tdap.
• Pregnant women should not receive live-vaccine.
• Severe combined immunodeficiency (SCID) as a contraindication to
rotavirus vaccine
Contraindications for vaccination
• The most common animal protein allergen is egg protein found in
vaccines prepared using embryonated chicken eggs (e.g. yellow fever
and influenza vaccines).

• Persons with histories of anaphylactic or anaphylactic-like allergy to

eggs or egg proteins should not receive such vaccines (YF and
influenza)
Vaccine storage

• The “cold chain” is the system of transporting and storing vaccines

within recommended temperature from the place of manufacture to
the point of administration.
• It has three main components:
• (1) personnel,
• (2) equipment, and
• (3) procedures
Vaccine storage

• The optimum temperature for refrigerated vaccines is between +2°C

and +8°C. For frozen vaccines, the optimum temperature is –15°C or
lower. In addition, protection from light is a necessary condition for
some vaccines.
VACCINE STORAGE EQUIPMENTS
• Walk-in Freezers
for bulk storage of OPV vaccines and also for preparation and storage of frozen ice
packs at state stores.
Maintain temperature of −18°C to −20°C.

• Walk-in Coolers
typically controlled between 2°C and 8°C.
Used for bulk storage of vaccines at state and regional stores.
• Walk-in coolers/walk-in freezers stores 3 months of requirement of vaccines and 25%
buffer stock for the districts they cater.
VACCINE STORAGE EQUIPMENTS

• Deep Freezers
Deep freezers have either top-opening lid or front door.
The cabinet temperature is maintained between –18°C and –20°C.
Used for storing of OPV at district and also for freezing ice packs.
• Ice-lined Refrigerator
Have a top opening.
keeps vaccine safe with as little as 8-hour continuous electricity supply in a
24-hour period.
Hence, it is suitable for use in the area with poor power supply.
Ice-lined refrigerator
Vaccine storage in ILR
Vaccine storage in cooler ILR
VACCINE STORAGE EQUIPMENTS

• Domestic Refrigerator
• Used by private hospitals.
• The domestic refrigerator is not designed for the special storage temperature
need of vaccines.
• For vaccine storage the domestic refrigerator has following drawbacks:
Temperature varies significantly every time the door is opened.
Temperature rises during defrosting
Cabinet temperature is easily affected by ambient temperature.
Temperature setting using dial is crude and inaccurate.
• Safe vaccine storage is possible in domestic refrigerators, if following points are
observed:
Store vaccine in a dedicated refrigerator especially for biologics. Do not store
food or drink in vaccine refrigerators.
The refrigerator compartment temperatures is maintained between 2°C and 8°C
and freezer compartment temperatures maintained at or below 5°F (−15°C).
The door seals are in good condition and are sealing tightly.
The door closes properly automatically on leaving it free.
The refrigerator has separate freezer compartment.
• Place measles, MR, MMR, BCG, OPV, yellow fever, Japanese
encephalitis (SA-14-142), meningococcal A conjugate, Rotavac*
and/or any other vaccines not damaged by freezing on the top shelf
• Put DTP, DT, Td, TT, Tdap, HepB, DTP+HepB, DTP+HepB+Hib, Hib, PCV,
HPV, Rotavirus and/or any other freeze-sensitive vaccines on the
middle or lower shelves.
• Rotavac can be stored at –20°C till expiry date. It can be stored upto 6
months at 2 to 8°C.
Storage protocol in domestic freeze
• Store the diluents next to the freeze-dried vaccine with which they
are supplied, on the appropriate shelf.
• If there is not enough space on the shelf, put the diluents on the
bottom shelf, clearly labeled so they can be easily identified to their
matching vaccine.
Vaccine Vial Monitor

• A vaccine vial monitor (VVM) is a label containing a heat-sensitive

material, which is placed on a vaccine vial to register cumulative heat
exposure over time

• The VVM is a circle with a small square inside it, which is lighter in
color than surroundings. The inner square of VVM is made of heat-
sensitive material that is lighter in color at the starting point. The
combined effect of time and temperature causes the inner square of
the VVM to darken gradually. The color change is irreversible
Whether or not to use the vaccine
ADVERSE EVENTS FOLLOWING IMMUNIZATION
(AEFI)

• Vaccines are among the safest medicines

• An AEFI is any untoward medical occurrence which follows immunization and

which does not necessarily have a causal relationship with the usage of the
vaccine, i.e. might have not been caused by vaccine ingredients or the process
of vaccination or immunization but have a temporal relationship with
administration of vaccine
• It can be any unfavorable or unintended sign, abnormal laboratory finding,
symptom, or disease. Sometimes, mass use of vaccines can cause anxiety in
community and even such responses can be considered as AEFI.
CAUSE-SPECIFIC TYPES OF
ADVERSE EVENT FOLLOWING
IMMUNIZATION
• Vaccine induced: caused by the intrinsic characteristic of the vaccine preparation
and the individual response of the vaccine; these events would not have occurred
without vaccination . Eg: BCG adenitis, DPT induced encephalopathy, VAPP
• Vaccine-potentiated: the events would have occurred anyway, but were
precipitated by the vaccination (Eg: first febrile seizure in a predisposed child)
• Programmatic error: the event was cause by technical errors in vaccine preparation,
handling or administration (eg: TSS d/t staphylococcal contamination of measles
vaccine)
• Immunization anxiety-related reaction: An AEFI arising from anxiety about the
immunization, e.g. vasovagal syncope in an adolescent following vaccination. The
anxiety may spread to community too, at times
• Co-incidental: happened by chance.
TYPES OF ADVERSE EVENTS FOLLOWING
IMMUNIZATIONS BASED ON SEVERITY

• Serious AEFI: An AEFI is considered serious if it (1) results in death, hospitalization,

or persistent or significant disability/incapacity, (2) occurs in clusters, (3) causes
parental/community concern, or (4) results in congenital anomaly/birth defect.
• Severe AEFI: Severe AEFIs are minor AEFIs with increased intensity/severity, e.g.
high grade fever following pentavalent vaccination or post-DPT swelling extending
beyond nearest joint. The patient may not be hospitalized and will not have
sequelae.
• Minor AEFI: Minor AEFIs can be local reactions (pain, swelling, and redness) or
systemic reactions (fever > 38°C, irritability, malaise, etc.), which can be managed
with antipyretics and anti-inflammatory and resolves within 2–3 days.
Vaccine hesitancy

• Vaccine hesitancy, the reluctance or refusal to vaccinate despite the

availability of vaccines,
Immunization in special
circumstances
I) Immunization in preterm infants
• All vaccines to be given except hepatitis B vaccine if weight < 2 kg if
mother is HBsAg negative. (decreased seroconversion in < 2kg)
• Vaccination postponed till baby attains weight > 2 kg.
• To be given if mother is HBsAg positive.
 II) Children with corticosteroids
• Low or moderate doses ( daily or on alternate days)
< 2mg/ kg per day of prednisone or its equivalent , or
< 20 mg/ day if they weigh more than 10 kg , can
receive live vaccines .
• High doses of systemic corticosteroid (daily or on
alternate days ) for fewer than 14 days > 2mg/ kg per day
of prednisone or its equivalent , or > 20 mg/ day if they
weigh more than 10 kg can receive live vaccine
immediately after discontinuation of treatment .
 II) Children with corticosteroids
• Live vaccines not to be given if on steroid ≥ 2mg/kg/day
for ≥14 days. To be given after one month of
discontinuation of steroid.
• Low potency Topical/local injection ,inhaled steroid is not
a contraindication for live vaccine
• Inactivated vaccines , if not given prior should to be given
to patients while receiving corticosteroid therapy
chronically.
III) Vaccination in HIV/AIDS
Asymptomatic Symptomatic
Vaccines
WHO AAP WHO AAP

BCG Y N N N
DPT Y Y Y Y
OPV Y N N N
Measles Y Y Y Y
Hib Y Y Y Y
Varicella Consider Consider Consider Consider
Hepatitis Y Y Y Y
B vaccine
Y = Yes, N = No , AAP=American Academic of Pediatrics
IV) Unknown / uncertain immunization
status
• Recommended immunization should be initiated
without delay on a schedule commensurate with the
person’s current age.

• No evidence suggests that administration of vaccines to

already immune recipients is harmful.
Immunization schedule for
unimmunized child
Age <7yrs >7 yrs

1st visit BCG, OPV, DPT, HBV Td, HBV

2nd visit (1 month later) DPT, OPV, HBV Td, HBV

3rd visit(1 month later) Measles or MMR, Typhoid MMR, Typhoid

4th visit (6 months after 1st DPT/ HBV HBV

visit)
V) Children with 1 ̊ & 2 ̊ Immune
Deficiencies

• Subspecialists for immunocompromised patients share

responsibility with the primary care physician for
ensuring appropriate vaccinations .
• Recommending appropriate vaccinations for members
of the patients household.
High-level immunosuppresion
• With combined B- and T- Lymphocyte primary immunodeficiency .
Eg Severe combined immunodeficiency (SCID)

• Receiving cancer therapy

• With HIV infection and CD4+ T-lymphocyte count<200 cell/mm3 for

> 5 years or a CD4+ T-lymphocyte percentage <15 % for infants and
children < 5 years
High-level immunosuppresion
• Receiving daily corticosteroid therapy ≥ 20 mg/day
( or > 2 mg/kg/day for patients weighing <
10 kg ) of prednisone or equivalent for ≥ 14 days .
• Receiving biologic immune modulators.
Eg : TNF-α antagonist ( infliximab , adalimumab,
certolizumab , etanercept , golimumab ) or anti- B-
lymphocyte monoclonal antibodies ( rituximab)
 High-level
immunosuppresion
• Within 2 months after solid organ transplantation (SOT)

• Within 2 months after hematopoietic stem cell

transplant ( HSCT ) ; longer for allogeneic than for
autologous
Low-level immunosuppression
• With HIV infection without symptoms and CD4+
T-lymphocyte counts of 200 to 499 cell/mm3 for >
5 years or a CD4+ T-lymphocyte percentage 15 % to
24 % for infants and children < 5 years

• receiving a lower daily dose of systemic corticosteroid

than for high-level immunosuppression for ≥ 14 days ,
or receiving alternate-day corticosteroid therapy.
Low-level immunosuppression
• Receiving methotrexate at a dosage of ≤ 0.4
mg/kg/week , azathioprine at a dosage of
≤ 3 mg/kg/day , 6- mercaptopurine at a dosage of
≤ 1.5 mg/ kg/day.
Timing of vaccines
• When immunosuppressive medication is planned ,
vaccination should be administered prior when feasible.
• Live vaccines should be administered ≥ 4 weeks prior to
initiation of immunosuppression and should not be
given within 2 weeks before initiation .
Timing of vaccines
• Inactivated vaccines should be administered ≥ 2 weeks prior to
immunosuppression.
• Inactivated and live virus vaccines can be given 3 months after
cessation of chemotherapy for acute leukemia
• MMR , varicella can be given after 24 months in HSCT.
Primary Immunodeficiencies
• All live – virus and inactivated vaccines can be given to children with
isolated IgA deficiency.
• Live and inactivated vaccine can be given in primary complement
deficiencies
• Leukocyte adhesion deficiency, Chediak-Higashi syndrome should be
given PCV 13 and then PPSV23 at ≥ 2 years age after 8 weeks after
PCV 13 followed by 2nd dose 5 years later.
Primary Immunodeficiencies
• Live- virus vaccine and all inactivated vaccines can be
given to Chronic granulomatous disease and cyclic
neutropenia

• Meninigococcal vaccine to complement deficiencies .

• Inactivated vaccines other than inactivated influenza

vaccine are not routinely given to patient with major
deficiencies or SCID during IG therapy.
Secondary ( Acquired)
immunodeficiencies
• Live-virus vaccines generally are contraindicated .
• Exception include in MMR and Varicella vaccine which
can be given to not severely immunosuppressed HIV
infected .
• Rotavirus vaccine are advised in infants exposed to or
infected with HIV
 vi) Asplenia and functional
asplenia

• 4 dose series of PCV13 , PPSV23 should be administered

a minimum of 8 weeks later, but only at the age of 24
months or older.
• Previously unimmunized children < 5years should
receive Hib vaccine according to the catch-up schedule.
Unimmunized children >5 years should receive single
dose of Hib vaccine.
 Asplenia and functional asplenia

• Quadrivalent meningococcal conjugate vaccine(MCV4)

should be administered to all children with asplenia
2 months or older.

• Revaccination with MCV4 3 years after the primary

series (PCV13) and then every 5 years for patient < 7
years , for patient > 7yrs initial booster dose should be
at 5 years following the primary series and then every
5 years thereafter.
Asplenia and functional asplenia
• MCV4-D( Menactra , Sanofi Pasteur) should be used after
4 weeks after completion of the PCV13 doses .

• If splenectomy is emergent , or vaccination was not

performed before splenectomy , indicated vaccination
should be initiated as soon as possible 2 weeks or more
after surgery.
 Splenectomy

Elective Emergency

At least 2weeks pre-operatively At least 2 weeks Post-operatively

PCV13 PCV13
PCV 23* PCV 23 *
HiB HiB
Meningococcal (MCV4) Meningococcal (MCV4)

• 8 weeks after PCV 13 for 2 years and above

 vii) Children with chronic
disease
• Immunization recommended as for healthy children .
• live-virus vaccines contraindicated in severe
immunologic disorders , including those receiving
chronic immunosuppressive therapy.
• HIV infected who are not severely immunocompromised
may receive MMR , varicella and rotavirus vaccines.
 viii) Solid organ transplantation
(SOT)

• Should receive all vaccinations as appropriate for age ,

exposure history and immune status as per national
immunization schedule .

• PCV13 doses followed by PCV23 ( 2 years and older) 8

weeks after the last PCV13 dose.
Solid organ transplantation
• Hepatitis B vaccine series in anti-HBs negative

• Hepatitis A vaccine in 12 months or older who did not receive

vaccination or seronegative .

• Living SOT donors and healthy household member should have up-to-
date vaccination status( including IIV).
 viii) CNS anatomic barrier
defects
• No vaccine is contraindicated.
• PCV 13 and PPSV23 should be administered ≥ 2 weeks
prior to cochlear implant surgery when feasible.
 Passive Immunization
• Immediate protection but for only a short period of
time.
• Peak serum concentrations obtained 2 to 3 days in IM
administration.
• IGIM administered to exposed , measles-susceptible
people will prevent or attenuate infection if
administered within 6 days of exposure.