ROSE MARIE TOMPONG-NAVAL, MD, FPPS

 To explain the principles of immunization

based on immunologic and biochemical
responses
 To classify the basic types of vaccines
 To discuss the general recommendations on
immunization
 To describe adverse reactions of
immunization
 To know and discuss the available vaccines
 To explain the principles of passive
immunization
 The process of inducing immunity against a
specific disease
 One of the most beneficial and cost-
effective disease prevention measures
available
---smallpox has been eradicated
---polio is close to worldwide eradication
(but we recently had cases of polio here in
the Philippines)
---measles and rubella no longer endemic in
the US (but there had been recent outbreaks of
measles, rubella and pertussis in the US and
even here in the Philippines)

---incidence of most vaccine-preventable

diseases has remarkably decreased
Comparison Of 20th Century Annual
Morbidity And Current Morbidity For
Vaccine-preventable Diseases
Disease 20th century 2016 Percent
annual reported decrease
morbidity cases
Smallpox 29,005 0 100%

Diphtheria 21,053 0 100%

Measles 530,217 122 >99%

Mumps 162,344 5,629 96%

Pertussis 200,752 15,808 92%

Polio (paralytic) 16,316 0 100%

Rubella 47,745 9 >99%

Congenital Rubella 152 2 99%

Tetanus 580 31 95%

Haemophilus 20,000 22 >99%

influenza
Comparison Of Pre Vaccine Era
Estimated Annual Morbidity With
Current Estimate For Vaccine-
Preventable Diseases
Disease Pre-vaccine era 2016 % decrease
annual estimate estimate

Hepatitis A 117,333 4,000 97%

Hepatitis B (acute) 66,232 20,900 68%

Pneumococcus –invasive
All ages 63,067 30,400 52%
<5yrs of age 16,069 1,700 89%

Rotavirus
(hospitalizations, <3 yrs) 62,500 30,625 51%

Varicella 4,085,120 102,128 98%

 Passive – administration of antibody-
containing preparations

 Active – administration of a vaccine or

toxoid to stimulate the immune system
to produce a prolonged humoral and/or
cellular immune response
 Administration of preformed antibodies

 Protection is immediate but transient (weeks

to months)

 To induce transient protection against an

infectious agent
 Products used include—

- immunoglobulin (Ig) given intramuscularly

(IGIM), intravenously (IGIV), subcutaneously
(IGSC)
- specific or hyperimmune globulin – IM, IV
- antibodies of animal origin
- monoclonal antibodies
 Transplacental transfer of maternal
antibodies (IgG) during pregnancy

 Protection may last for 1 month and

longer during breastfeeding

 Protection lasts for one year in some

diseases depending on the quantity of
antibody transferred
Major indications –

 Immunodeficient children with B-lymphocyte

defects, can’t make their own antibodies

 People exposed to infectious diseases

 Imminent risk of exposure, not enough time

to develop an active immune response to a
vaccine

 Part of specific therapy of an infectious

disease
 Sterile antibody-containing solution, derived
from human plasma
 Contains 15-18% proteins
 Predominantly IgG

 Major indications:
◦ Replacement therapy for antibody deficiency
disorders
◦ Measles prophylaxis
◦ Hepatitis A prophylaxis
IM IMMUNOGLOBULIN

Replacement therapy –

◦ 100mg/kg or 0.66 ml/kg monthly

◦ Usual interval between doses is 2-4 weeks

◦ IVIG has replaced IM Ig for replacement therapy

IM IMMUNOGLOBULIN

 Measles prophylaxis – 0.5 ml/kg, max 15 ml,

administered within 6 days of exposure

 Recommended dose for IVIG is 400 ml/kg

 Measles vaccine if given within 72 hrs of

exposure may provide protection

 Measles vaccine and immunoglobulin should

not be administered at the same time
IM IMMUNOGLOBULIN

 Hepatitis A prophylaxis – post

exposure and people travelling to
endemic areas

◦ 12 months to 40 years – hepatitis A vaccine

is preferred over immunoglobulin

◦ Less than 12 months and more than 40

years – 0.06 ml/kg
 Most common adverse reactions –
◦ Pain and discomfort at injection site
◦ Flushing, headache, chills, nausea

Serious adverse reactions - chest pain,

dyspnea, anaphylaxis, systemic collapse
 Hepatitis B immunoglobulin IM – post
exposure prophylaxis, prevention of perinatal
infection in infants born to hepatitis B surface
antigen-positive mothers

 Rabies immunoglobulin IM – post exposure

prophylaxis

 Tetanus immunoglobulin IM – wound

prophylaxis, treatment of tetanus
 Varicella-zoster immunoglobulin IM or IVIG –
postexposure prophylaxis of susceptible people
at high risk for complications from varicella

 Cytomegalovirus IVIG – prophylaxis of disease in

seronegative transplant recipients

 Vaccinia immunoglobulin IV – prevent or modify

serious adverse events following smallpox
vaccination caused by vaccinia replication
 Highly purified preparation of
immunoglobulin antibodies

 More than 95% IgG

 Replacement therapy for primary
immunodeficiency disorders

 Kawasaki disease to prevent coronary

artery abnormalities and shorten clinical
course

 Replacement therapy for prevention of

serious bacterial infections in HIV
 Prevention of serious bacterial infections in
hypogammaglobulinemia in chronic B
lymphocyte leukemia

 Immune-mediated thrombocytopenia to
increase platelet count

 Prophylaxis following bone marrow

transplantation
 Severe toxic shock syndrome

 Guillian-Barre syndrome

 Anemia due to parvovirus B19

 Varicella post-exposure
 Up to 25%, may be related to the rate of
infusion

 Fever, headache, myalgia, nausea,

vomiting, chills
 Anaphylactoid events, thromboembolic
disorders, aseptic meningitis, renal
insufficiency - rare

 Renal failure in those with preexisting renal

dysfunction
 Safe and effective – in primary immune
deficiency disorders
 Smaller doses administered weekly
 Less frequent systemic reactions than
with IVIG
 Most common adverse effect – injection
site reactions
 Derived from horses

 Two equine antisera preparations:

◦ Diphtheria antitoxin – treatment of diphtheria,
can be obtained from CDC
◦ Heptavalent (A-G) botulinum antitoxin –
treatment of food & wound botulism, used for
adults – CDC

* for infant botulism, IVIG (BabyBIG), a human-

derived antitoxin is available
 Potential for severe allergic reactions

 Test for sensitivity before administration

 Desensitization

 Potential reactions – febrile events, serum

sickness, anaphylaxis
 Antibody preparations against a single
antigen

 Mass produced from a hybridoma –

created by fusing an antibody producing
B lymphocyte with a fast-growing
immortal cell
 Palivizumab – prevents severe disease from
respiratory syncytial virus (RSV) among
children 24 mos and younger with chronic
lung disease

 Prevent transplant rejection

 Treatment of malignant and autoimmune

diseases and asthma
 15 mg/kg IM once a month – RSV season

 Infants born before 20 wks of gestation in the 1st

year of life

 Infants born before 32 wks of gestation who

have chronic lung disease of prematurity in the
1st year of life

 Infants younger than I yr of age with

hemodynamically significant congenital heart
disease
 Immunocompromised children 24 months or
younger

 Infants in the 1st yr of life with congenital

abnormalities of the airway or neuromuscular
disease

 During the 2nd yr of life for children who

required 28 days or more of oxygen after
birth
Vaccines – whole or part of
microorganisms administered to prevent
an infectious disease

◦ Whole or inactivated – IPV, hepatitis A

◦ Parts of the organism – acellular pertussis,

HPV, hepatitis B

◦ Polysaccharide capsules – pneumococcal,

meningococcal polysaccharide vaccines
◦ Polysaccharide capsules conjugated to
protein carriers – Hib, pneumococcal,
meningococcal

◦ Live attenuated – measles, MMR, varicella,

rotavirus, influenza

◦ Toxoids –bacterial toxin rendered

nontoxic but can induce an immune
response- tetanus, diphtheria
 Suspending fluids – sterile water or saline, or
complex fluid which may contain proteins

 Preservatives, stabilizers & antimicrobials –

inhibit bacterial growth & prevent
degradation of the antigen (gelatin, 2-
phenoxyethanol, antimicrobial agents)
- usually added to multidose vials
- thimerosal, contain ethyl mercury
 Adjuvants- enhance the immune response,
aluminum salts and arsenate licensed by FDA
- should be injected deep IM to avoid local
irritation, granuloma formation and
necrosis

*immunizing antigen
 Induce immunity by stimulating antibody
formation, cellular immunity or both

 Mediated primarily by B lymphocytes, which

produce antibodies- inactivate toxins,
neutralize viruses and prevent their
attachment, facilitate phagocytosis and killing
the bacteria
 Most B lymphocyte responses require the
assistance of CD4 helper T lymphocytes

 T lymphocyte-dependent responses tend to

induce high levels of functional antibodies, good
response even in infants

 T lymphocyte-independent vaccines – poor

immune response in children <2yrs, short term
immunity, no enhanced or booster response to
repeat exposure to antigen
-polysaccharide vaccines
 Polysaccharides have been conjugated to
protein carriers – converting the vaccine to a
T-lymphocyte dependent vaccine

◦ Higher-avidity antibody
◦ Immunologic memory leading to booster response
to repeated exposure
◦ Long-term immunity
◦ Herd protection by decreasing carriage of the
organism
◦ E.g. Hib, pneumococcal, meningococcal
 Serum antibodies can be detected 7-10days
after injection

 Early antibodies – IgM class

 IgM antibodies tend to decrease as IgG

antibodies increase

 IgG tend to peak 1 month after injection

 Serum antibodies can be measured to assess

immune response
 Measles, mumps, rubella – MMR

 MMR and varicella – MMRV

 Rotavirus

 Varicella

 Live attenuated influenza vaccine (LAIV)

 Yellow fever
-induce long-term immune response

-administered in 1 or 2 dose schedules

-2nd dose of MMR- to induce a primary

immune response in those who failed to
respond to the 1st dose
 Require multiple doses
 Need booster doses to maintain the immunity

 Hepatitis A – whole virus

 Japanese encephalitis – whole virus that is
purified
 Poliomyelitis (enhanced potency, IPV) – whole
virus
 Rabies vaccine (human diploid and purified
chick embryo cell) – whole virus
 Diphtheria and tetanus toxoid and acellular
pertussis (DTaP)
 DTaP-Inactivated polio vaccine - tetravalent
 DTaP–Inactivated polio vaccine-H. influenza
type B - pentavalent
 DTaP-Inactivated polio vaccine-H. influenza
type B-Hepatitis B –hexavalent
 Tetanus and diphtheria toxoids adsorbed
plus acellular pertussis (Tdap)
 Bacille Calmette-Guerin (BCG) – Live-
attenuated mycobacterial strain, to prevent
tuberculosis in very limited circumstances

 Human papilloma virus vaccine HPV –

◦ Bivalent – L1 capsid proteins of HPV types 16 & 18
◦ Quadrivalent – HPV types 6, 11 (warts) 16 & 18 for
cervical cancer
◦ 9valent– HPV types 6, 11, 16, 18, 31, 33,45, 52, 58
 Pneumococcal – 23valent (PPSV23) – 23
serotypes for 85-90% of bacteremic diseases
in the US

 Meningococcal – serogroups A, C, W135, Y

 Pneumococcal conjugated to a nontoxic form
of diphtheria toxin CRM 197 – 13 valent
PCV13, contain 13 serotypes that accounted
for more than 80% of invasive disease in
young children

 Meningococcal conjugate vaccine

Characteristic Conjugate Polysaccharide
T-lymphocyte dependent immune Yes No
response

Immune memory Yes No

Persistence of protection Yes No
Booster effect Yes No
Reduction of carriage Yes No
Herd protection Yes No

Lack of hyporesponsiveness Yes No

 Intradermal
 Given at birth or within first 2 months
 PPD prior to BCG is recommended in –
◦ Suspected congenital TB
◦ History of close contact to known or suspected
infectious cases of TB
◦ Clinical findings suggestive of TB and/or chest x-
ray suggestive of TB
 Affords approximately 80% protection against
TB meningitis and miliary TB in infancy and
young children

 Possible reactions –
◦ Keloid scar formation
◦ Suppurative regional adenitis
◦ Disseminated BCG infection
◦ Osteomyelitis
 Intramuscular
 First dose given within 24 hrs of life
 Birth dose may be used as 1st dose in a 3-
dose primary series
 Doses are given at least 4 weeks apart
 Fourth dose needed –
◦ If 3rd dose is given <24weeks of age
◦ Preterms <2kg

Possible reactions – soreness, erythema, swelling

Close to 100% efficacy
 Intramuscular

 Starting 6 weeks of age, may be given as

early as 4 weeks in outbreaks/epidemics

 Primary series – 3doses given at 6, 10, 14

weeks or 2, 4, 6 months

 Booster doses given 1 yr after the last dose of

primary series and between 4-6 yrs of age
 Endotoxin component of the whole cell
pertussis vaccine causes neuroparalytic
reactions

 Other reactions – fever, restlessness,

irritability, local signs of inflammation

 Almost 100% efficacy

 Confers 10 yrs immunity

2 forms available –
◦ Live attentuated trivalent oral polio (OPV or Sabin)
◦ Inactivated polio (IPV or Salk)

Indications for IPV:

◦ immunocompromised persons who are
unimmunized or partially immunized
◦ Household contacts of immunodeficient
individual
◦ Unimmunized adults at future risk of exposure to
poliomeylitis

More than 95% efficacy

Lifelong immunity
 Subcutaneous
 Given at 9 months, or as early as 6 months
during outbreaks
 Booster doses at 12 months and 4-6 yrs old
as MMR
 Possible reactions: fever, rash 5-10 days after
 95% efficacy
 Intramuscular
 Starting 6 weeks of age, may be given
together with DPT
 Primary series – 3doses given at 6, 10, 14
weeks or 2, 4, 6 months
 Booster dose given 1 yr after the last dose
 Given to children up to 5 yrs
 Given to children older than 5 yrs who have
◦ Sickle cell disease
◦ Leukemia
◦ HIV infection
◦ Hodgkin’s disease
◦ Post-splenectomy

Possible reactions – pain, redness, swelling, fever,

irritability

90-100% effective
 Subcutaneous
 1 year of age
 Repeat dose at 4-6yrs old but may be given
earlier
 More than 95% efficacy
 Long lasting immunity, probably lifetime
 Possible reactions
 Due to measles component – fever, rash 5-10
days after dose
 Due to mumps component – febrile seizures,
nerve deafness, encephalitis, rash, pruritus
 Due to rubella component – arthralgia,
lympadenopathy, mild rash 2-4 weeks after
dose
 Oral
 Monovalent human rotavirus (RV1) – 2doses
 Pentavalent human bovine rotavirus vaccine
(RV5) – 3 doses
 First dose of RV1 must be given 6-20 wks of
age
 First dose of RV5 must be given 6 wks -
14wks and 6days
 Last dose should be given not later than 32
wks
 85-95% efficacy
 Intramuscular
 PCV – 6 weeks minimum age – 3 doses+1
 PPV – 2 years, revaccination after the 1st dose
◦ Chronic heart, lung and kidney disease
◦ Chronic renal failure
◦ CSF leak
◦ Cochlear implant
◦ Sickle cell disease and other hemoglobinopathies
◦ Anatomic or functional asplenia
◦ HIV & congenital immunodeficiency
◦ Immunosuppression
◦ Solid organ transplant
 10valent – serotypes 4, 6B, 9V, 14, 18C, 19F,
23F, 1, 5, 7F
 13valent – serotypes 4, 6B, 9V, 14, 18C, 19F,
23F, 1, 5, 7F, 3, 6A, 19A

 Primary series – 3 doses at 4-8weeks interval,

plus a booster dose at 6 months after the 3rd
dose
 Intramuscular
 Primary vaccination – 3 doses, minimum age
9 yrs
 Subcutaneous
 Minimum age of 9 months, booster dose
after 12-24 months
 18 yrs or older – 1 dose
 Subcutaneous
 First dose at 12-15 months
 Second dose at 4-6 years or at an earlier age
provided the interval between the 2 doses is
at least 3 months
 For 13 yrs and older – 2 doses at least 4 wks
apart
 Possible reactions – fever, maculopapular
eruptions in 3%
 Close to 100% efficacy
 Intramuscular
 First dose given at 12 months
 2nd dose given 6 months after the 1st dose
 99% effective
 Intramuscular
 7-18 years of age who are not fully
immunized with DPT should be given a single
dose
 Td booster given every 10 years
 Almost 100% efficacy
 10 years immunity
 Intramuscular (quadrivalent)
 IM/SC (trivalent)
 6-35 months – 0.25 ml
 36 months to adults – 0.5 ml
 High risk conditions:
◦ Chronic cardiovascular disease
◦ Chronic metabolic and renal disorders
◦ Chronic lung disease – asthma
◦ Hemoglobinopathies
◦ Long term aspirin therapy
 Children 6 months to 8 years receiving
influenza vaccine for the first time should
receive 2 doses of the vaccine given at least 4
weeks apart initially then one dose yearly
 Children 6-18 years – annual dose
 Children who received only 1 dose of
influenza vaccine in the first year of life
should receive 2 doses the following year
 90% efficacy
 1 year immunity
Thank you