VACCINATION

PRINCIPLES OF VACCINATION
• Protection from infectious disease
• Usually indicated by the presence of antibody
• Very specific to a single antigen
• Perlindungan dari penyakit menular
• Biasanya ditandai dengan adanya antibodi
• Sangat spesifik untuk antigen tunggal
 PRINCIPLES OF VACCINATION
Active Immunity
• Protection produced by the person's own immune
system
• Usually permanent

Passive Immunity
• Protection transferred from another person or
animal as antibody
• Temporary protection that wanes with time
• Vaccination stimulates the immune system with a particular
agent (e.g. bacterium, virus, toxin) causing it to develop
antibody against it and produces immunological memory.

• Anything that stimulates an immune response, whether

naturally or via vaccination is called an antigen.

• Vaccinated individuals produce a much stronger immune

response if they encounter the agent again and will have a
much lower chance of developing disease.
• Vaksinasi menstimulasi sistem kekebalan dengan agen
tertentu (mis. Bakteri, virus, toksin) yang
menyebabkannya mengembangkan antibodi terhadapnya
dan menghasilkan memori imunologis.

• Apa pun yang merangsang respons imun, baik secara

alami atau melalui vaksinasi disebut antigen.

• Orang-orang yang divaksinasi menghasilkan respons imun

yang jauh lebih kuat jika mereka menghadapi agen lagi
dan akan memiliki peluang lebih rendah untuk terserang
penyakit.
Types of immune responses:
• Cell-mediated
specific cells called cytotoxic T cells attack cells in the body that have
become infected, and
• Humoral
body develops antibodies that neutralize and help eliminate antigens in
the blood, on epithelial surfaces and in tissues fluid
Jenis respons imun:
Dimediasi sel
sel spesifik yang disebut sel T sitotoksik menyerang sel dalam tubuh yang telah
terinfeksi, dan
Humoral
tubuh mengembangkan antibodi yang menetralkan dan membantu menghilangkan antigen
dalam darah, pada permukaan epitel dan cairan jaringan
Antigen

 A live or inactivated substance capable of producing an immune

response
 Single constituent,e.g., polysaccharide or tetanus, diphteria
 Complex constituent (live viruses , killed pertussis bacteria)
Antibody

• Protein molecules (immunoglobulin) produced by B lymphocytes to

help eliminate an antigen
Antigen- Zat hidup atau tidak aktif yang mampu menghasilkan respons imun
Konstituen tunggal, mis., Polisakarida atau tetanus, difteri
Konstituen kompleks (virus hidup, membunuh bakteri pertusis)

Antibody- Molekul protein (imunoglobulin) diproduksi oleh limfosit B untuk membantu

menghilangkan antigen
PASSIVE IMMUNITY
• Transfer of antibody produced by one human or other animal to
another
• Transplacental most important source in infancy
• Temporary protection
• Transfer antibodi yang diproduksi oleh satu manusia atau hewan
lain ke yang lain
• Sumber transplasental yang paling penting pada masa bayi
• Perlindungan sementara
SOURCES OF PASSIVE IMMUNITY
• Almost all blood or blood products
• Homologous pooled human antibody (immune globulin)
• Homologous human hyperimmune globulin
• Heterologous hyperimmune serum (antitoxin)
• Hampir semua darah atau produk darah
• Antibodi manusia yang dikumpulkan secara homolog (globulin
imun)
• Globulin hiperimun manusia homolog
• Serum hiperimun heterolog (antitoksin)
 PASSIVE IMMUNIZATION
• Passive immunization is the administration of preformed
antibodies either intravenously or intramuscularly.
• It is used to provide rapid protection in certain infections
such as diptheria or tetanus or in the event of accidental
exposure to certain pathogens such as hepatitis B.
• It is also used to provide protection in immune compromised
individuals.
Imunisasi pasif adalah pemberian antibodi preformed baik secara intravena atau intramuskuler.
Ini digunakan untuk memberikan perlindungan cepat pada infeksi tertentu seperti diptheria atau
tetanus atau jika terpapar secara tidak sengaja terhadap patogen tertentu seperti hepatitis B.
Ini juga digunakan untuk memberikan perlindungan pada individu dengan kekebalan tubuh yang
lemah.
 PASSIVE IMMUNIZATION

Infection Source of Antiserum Indications

Tetanus Immune human; horse Post exposure (plus vaccine)

Diptheria Horse Post-exposure

Gas gangrene Horse Post-exposure

Botulism Horse Post-exposure

Varicella-Zoster Immune human Post-exposure in immunodeficiency

Rabies Immune human Post exposure (plus vaccine)

Hepatitis B Immune human Post-exposure prophylaxis

Hepatitis A Pooled human Ig Prophylaxis

Measles Immune human Prophylaxis

Snakebite Horse Post-bite

Some autoimmune disease Pooled human ig Acute thrombocytopenia and

neutropenia
VACCINATION
• Active immunity produced by vaccine

• Immunity and immunologic memory similar to natural infection

but without risk of disease
• Kekebalan aktif yang dihasilkan oleh vaksin
• Kekebalan dan memori imunologis mirip dengan infeksi alami
tetapi tanpa risiko penyakit
 ACTIVE IMMUNIZATION

• Active immunization is the administration of vaccines containing

microbial products with or without adjuvants in order to obtain long
term immunological protection against the offending microbe.
• At present the normal route of vaccination in most instances is either
intramuscularly or subcutaneously.
• Oral immunization is the method of choice for polio and Salmonella
typhi vaccines --- may be the best for most immunizations since
nearly all infectious agents gain entrance through the mucosal
surfaces.
• Imunisasi aktif adalah pemberian vaksin yang
mengandung produk mikroba dengan atau tanpa bahan
pembantu untuk mendapatkan perlindungan imunologi
jangka panjang terhadap mikroba yang menyinggung.
• Saat ini rute normal vaksinasi dalam banyak kasus adalah
secara intramuskular atau subkutan.
• Imunisasi oral adalah metode pilihan untuk vaksin polio
dan Salmonella typhi --- mungkin yang terbaik untuk
sebagian besar imunisasi karena hampir semua agen
infeksi dapat masuk melalui permukaan mukosa.
 General Rule
• The more similar a vaccine is to the natural disease, the better
the immune response to the vaccine
• Inactivated vaccines are generally not affected by
circulating antibody to the antigen.
• Live attenuated vaccines may be affected by circulating
antibody to the antigen.
• Vaksin yang lebih mirip dengan penyakit alami, semakin baik respons imun
terhadap vaksin

• Vaksin yang tidak aktif umumnya tidak terpengaruh oleh sirkulasi antibodi terhadap
antigen.

• Vaksin yang dilemahkan langsung dapat dipengaruhi oleh sirkulasi antibodi

terhadap antigen.
 EFFECTIVE VACCINES ARE:
• Safe
• Aman
• Protective for sustained period
• Pelindung untuk periode berkelanjutan
• Induce neutralising antibody
• Menginduksi antibodi penawar
• Biologically stable
• Stabil secara biologis
• Cheap to produce
• Murah untuk diproduksi
• Easy to administer
• Mudah dikelola
• Berikan kekebalan seumur hidup
• Lebih disukai dosis tunggal
• Keamanan
• Bahaya kembalinya ke virulensi atau penyakit parah pada
imuno yang dikompromikan
• Stabilitas
• Organisme dalam vaksin harus tetap hidup agar dapat
menginfeksi dan mereplikasi inang
• Persiapan vaksin harus kurang sensitif terhadap kondisi
penyimpanan yang buruk
• Biaya
THE DEVELOPMENT OF VACCINES

• First generation—whole - organism vaccines-

- Inactivated/Killed,
-live attenuated
• Second generation
• subunit vaccine,
• recombinant antigen Vaccine,,
• synthetic peptide vaccines

• Third generation----DNA vaccine

• Generasi pertama — seluruh - vaksin organisme- - Tidak
aktif / Dibunuh,
• -Live dilemahkan
• Generasi kedua
• vaksin subunit,
• Vaksin antigen rekombinan ,,
• vaksin peptida sintetis

• Generasi ketiga ---- vaksin DNA

 CLASSIFICATION OF VACCINES
Currently available vaccines are either:
Vaksin yang tersedia saat ini adalah:
• Live (attenuated/ weakened)
Langsung (dilemahkan / dilemahkan)
• Killed or Inactivated
Dibunuh atau Tidak Aktif
• Fractionated
Difraksinasi
• Recombinant Live attenuated
Rekombinan Hidup dilemahkan
22
 INACTIVATED VACCINES
Whole
• virus
• bacteria
Fractional

• protein-based
• subunit
• toxoid
• polysaccharide-based
• pure
• conjugate
 LIVE ATTENUATED VACCINES
• Attenuated (weakened) form of the "wild" virus or bacteria
• Must replicate to be effective
• Immune response similar to natural infection
• Usually effective with one dose* (per oral)
• Severe reactions possible
• Interference from circulating antibody
• Unstable
• Bentuk virus atau bakteri "liar" yang dilemahkan (dilemahkan)
• Harus meniru agar efektif
• Respon kekebalan mirip dengan infeksi alami
• Biasanya efektif dengan satu dosis * (per oral)
• Reaksi yang parah mungkin terjadi
• Gangguan dari antibodi yang bersirkulasi
• Tidak stabil
 LIVE ATTENUATED VACCINES

• Viral : measles, mumps,

rubella, vaccinia,
varicella, yellow fever,
influenza, (oral polio)
(rotavirus)
campak, gondong, rubella, vaccinia, varicella, demam kuning,
influenza, (polio oral) (rotavirus)
• Bacterial: BCG, oral typhoid
• Cannot replicate
• Minimal interference from circulating antibody
INACTIVATED VACCINES
• Generally not as effective as live vaccines
• Generally require 3-5 doses
• Immune response mostly humoral
• Antibody titer diminishes with time
Tidak bisa meniru
Gangguan minimal dari sirkulasi antibodi
Umumnya tidak seefektif vaksin hidup
Umumnya membutuhkan 3-5 dosis
Respon imun sebagian besar humoral
Titer antibodi berkurang seiring waktu
 INACTIVATED VACCINES
Whole cell vaccines

• Viral : polio, hepatitis A, rabies, influenza

• Bacterial: pertussis, typhoid, cholera

Fractional vaccines

• Subunit: hepatitis B, influenza, pertussis, lyme

• Toxoid: diphtheria, tetanus
ATTENUATION VS. INACTIVATION
POLYSACCHARIDE VACCINES
Pure polysaccharide

• pneumococcal
• meningococcal
• Salmonella Typhi (Vi)
Conjugate polysaccharide

• Haemophilus influenzae type b

• pneumococcal
 PURE POLYSACCHARIDE VACCINES

• Not consistently immunogenic in children <2 years of age

• No booster response
• Antibody with less functional activity
• Immunogenicity improved by conjugation
Imunogenik tidak konsisten pada anak-anak <2 tahun
Tidak ada respons penguat
Antibodi dengan aktivitas yang kurang fungsional
Imunogenisitas membaik dengan konjugasi
 SUCCESSFUL VACCINES

• Activate antigen-presenting cells to initiate antigen processing and

produce cytokines
• Activate both T and B cells to give a high yield of memory cells
• Generate Th and Tc cells to several epitopes, to overcome the variation
in the immune response in the population due to MHC polymorphism
• Enable the persistence of antigen, probably on follicular dendritic cells in
lymphoid tissue, to elicit continued production of antibody from B cells.
• Whole organism vaccines tend to have these abilities. Subunit vaccines
can be enhanced to produce these results by the use of adjuvants
• Aktifkan sel penyaji antigen untuk memulai pemrosesan
antigen dan memproduksi sitokin
• Aktifkan kedua sel T dan B untuk memberikan hasil tinggi
sel memori
• Hasilkan sel Th dan Tc ke beberapa epitop, untuk
mengatasi variasi dalam respon imun dalam populasi
akibat polimorfisme MHC
• Memungkinkan persistensi antigen, mungkin pada sel
dendritik folikuler dalam jaringan limfoid, untuk
memperoleh produksi antibodi dari sel B yang
berkelanjutan.
• Vaksin organisme utuh cenderung memiliki kemampuan
 CONTENT OF VACCİNES

Component
• Prezervatives
• Stabilizers
• Antibiotics
• Adjuvants
• Suspending fluids
• Complex fluids
egg yolk antigen,
substances in tissue culture,
serum proteins)
Functions
Prevent bacterial growth
Stabilize the antigen
Neomycin, Streptomycin
Enhances immunogenecity
Aluminum hydroxide
Sterile water or sal
•Component
Prezervatif Mencegah pertumbuhan bakteri
Functions
• Stabilisator Menstabilkan antigen
• Antibiotik Neomycin, Streptomycin
• Adjuvan Meningkatkan imunogenesis
• Aluminium hidroksida
• Cairan suspensi Air steril atau garam
• Cairan kompleks
• antigen kuning telur,
• zat dalam kultur jaringan,
 PRESERVATİVES

• Tiomersal : DT, dT, TT, İnfluenzae

Pneumococcal polysaccharide(Wyett)
• 2-phenoxietanol ve formaldehide : IPV
• Phenol : Tifo Vi, Pneumococcal polysaccharide
(pasteur)
• Benzetonium chlorur(femerol): Şarbon
• 2-phenoxyetanol: DBaT (Infanrix, GSK)
Hepatitis A (Havrix, GSK)
Hepatitis A/B(Twinrix, GSK)
Lyme (Lymerix, GSK)
 Vaccine Additives

Antibiotics – prevent growth of contaminating bacteria

Aluminum gels/salts – adjuvant that stimulates a greater immune
response
Egg protein – vaccines prepared in eggs; not suitable for allergic
persons; e.g., most influenza vaccines
Thiomerosal – mercury-containing preservative
Antibiotik - mencegah pertumbuhan bakteri yang terkontaminasi
Gel / garam aluminium - bahan pembantu yang merangsang respons imun yang lebih
besar
Protein telur - vaksin yang disiapkan dalam telur; tidak cocok untuk orang alergi; mis.,
sebagian besar vaksin influenza
Thiomerosal - pengawet yang mengandung merkuri
ATTENUATED AND İNACTİVATED VACCİNE

Properties Attenuated Vaccine Inactivated Vaccine

Preparation Virulent strain, Pathogen,

various culture inactivated by
medium, long chemicals or
passages gamma radiation
Booster Just one More than one

Stabilization NOT GOOD BETTER stabilized

Immune response Humoral and Humoral

cellular
Adjuvant name Compositions Mechanism of action
Freund’s incomplete Oil-in- emulsion Delayed release of antigen,
adjuvant Enhanced uptake by macrophages
Freund’s complete Oil-in- water with Delayed release of antigen,
adjuvant dead Mycobacteria Enhanced uptake by macrophages
Induction of co-stimulators in
macrophages
Freund’s adjuvant Oil-in- water with Delayed release of antigen,
With MDP Muramyldipeptid Enhanced uptake by macrophages
Induction of co-stimulators in
macrophages
Alum Aluminum Hidroxide Delayed release of antigen,
gel Enhanced uptake by macrophages
Alum+B.pertussis Aluminum Hidroxide Delayed release of antigen,
gel with Enhanced uptake by macrophages
Killed B.pertussis Induction of co-stimulators in
macrophages
Immun stimulatory Matrix of lipid micelles Delivers antigen to cytosol
complexes(ISCOM) containing Viral proteins İnduction of Cytotoxic T cells
• Allergic VACCINE ADVERSE REACTIONS
• due to vaccine or vaccine
component
• rare
• risk minimized by screening
Alergi
karena vaksin atau komponen vaksin
langka
risiko diminimalkan dengan penyaringan
 PRECAUTION
• A condition in a recipient that might increase the chance or
severity of an adverse reaction, or

• Might compromise the ability of the vaccine to produce

immunity
• Suatu kondisi pada penerima yang dapat meningkatkan
kemungkinan atau tingkat keparahan reaksi yang
merugikan, atau
• Mungkin membahayakan kemampuan vaksin untuk
menghasilkan kekebalan
CONTRAINDICATIONS AND PRECAUTIONS

Permanent contraindications to
vaccination:
• severe allergic reaction to a vaccine
component or following a prior dose

• encephalopathy not due to another

identifiable cause occurring within 7 days of
pertussis vaccination
INVALID CONTRAINDICATIONS TO VACCINATION
• Mild illness
• Antimicrobial therapy
• Disease exposure or convalescence
• Pregnant or immunosuppressed person in the household
• Breastfeeding
• Preterm birth
• Allergy to products not present in vaccine or allergy that is not anaphylactic
• Family history of adverse events
• Tuberculin skin testing
• Multiple vaccines
• Penyakit ringan
• Terapi antimikroba
• Paparan penyakit atau pemulihan
• Orang hamil atau yang tertekan sistem imun di rumah
tangga
• Menyusui
• Kelahiran prematur
• Alergi terhadap produk yang tidak ada dalam vaksin atau
alergi yang bukan anafilaksis
• Riwayat keluarga dari kejadian buruk
• Tes kulit tuberkulin
 VACCINATION OF PREGNANT WOMEN
• Live vaccines should not be administered to women known to be
pregnant
• In general inactivated vaccines may be administered to pregnant
women for whom they are indicated
• Vaksin hidup tidak boleh diberikan kepada wanita yang diketahui
hamil
• Secara umum, vaksin yang tidak aktif dapat diberikan kepada
wanita hamil untuk siapa mereka diindikasikan
VACCINATION OF IMMUNOSUPPRESSED
PERSONS
• Live vaccines should not be administered to severely
immunosuppressed persons
• Inactivated vaccines are safe to use in immunosuppressed
persons but the response to the vaccine may be decreased
• Vaksin langsung tidak boleh diberikan kepada orang yang sangat
imunosupresi
• Vaksin yang tidak aktif aman digunakan pada orang yang
kekurangan imun tetapi respons terhadap vaksin mungkin
menurun
 VACCINATION DURING ACUTE ILLNESS
• No evidence that acute illness reduces vaccine efficacy or
increases vaccine adverse reactions
• Vaccines should be delayed until the illness has improved
• Mild illness, such as otitis media or an upper respiratory
infection, is NOT a contraindication to vaccination
• Tidak ada bukti bahwa penyakit akut mengurangi kemanjuran vaksin atau meningkatkan
reaksi merugikan vaksin
• Vaksin harus ditunda sampai penyakitnya membaik
• Penyakit ringan, seperti otitis media atau infeksi saluran pernapasan atas, BUKAN
merupakan kontraindikasi untuk vaksinasi
 Vaccine Characteristics
vaksin yang tidak aktif
Inactivated vaccines
Respon imun terbatas
Limited immune response
Kekebalan mungkin berkurang dari waktu ke
Immunity may wane over time waktu
No secondary spread Tidak ada penyebaran sekunder
Live vaccines Vaksin hidup
Replicate in vivo Replikasi in vivo
Induce larger immune response Induksi respon imun yang lebih besar
Induce immune memory/recall Induksi daya ingat / daya ingat
Can revert to virulence Dapat kembali ke virulensi
Can be secondarily transmitted to others Dapat ditransmisikan secara sekunder ke
orang lain
 Routes of Administration
Intramuscular Intramuskular
Stimulates systemic immunity Merangsang kekebalan sistemik
May induce injection reactions Dapat memicu reaksi injeksi
Subcutanecous Subkutan
Oral Oral
Easily administered Mudah dikelola
Induces gastric mucosal and systemic Menginduksi imunitas mukosa lambung dan
immunity sistemik
Nasal Nasal
Easily administered Mudah dikelola
Induces nasal mucosal and systemic Menginduksi imunitas mukosa hidung dan
immunity sistemik
• Protection against pathogenic microorganisms require the
ANTIGEN PREPARATIONS
generation of effective immune mechanisms.
• Thus, vaccines must be capable of targeting the immune system
appropriately i.e. cellular / or humoral mechanisms.
• Most vaccines consist of either attenuated organisms, killed
organisms, inactivated toxins, or subcellular fragments and more
recently genes for antigens in viral ‘vectors’, and DNA itself.
• Perlindungan terhadap mikroorganisme patogen membutuhkan
pembentukan mekanisme imun yang efektif.
• Dengan demikian, vaksin harus mampu menargetkan sistem
kekebalan dengan tepat yaitu mekanisme seluler / atau humoral.
• Sebagian besar vaksin terdiri dari organisme yang dilemahkan,
organisme yang dibunuh, toksin yang tidak aktif, atau fragmen
subseluler dan baru-baru ini gen antigen dalam 'vektor' virus, dan
DNA itu sendiri.
 ANTIGEN PREPARATIONS USED IN VACCINES
Type of antigen Examples
Viruses Bacteria
Normal heterologous organism Vaccinia (Cowpox)
Living attenuated organism Measles BCG
Mumps Typhoid (New)
Rubella
Polio (Sabin)
Yellow fever
Varicella-Zoster
Whole killed oranism Rabies Pertussis
Poli (Salk) Typhoid
Influenza Cholera
Subcellular fragment
Inactivated toxin (toxoid) Diphtheria
Tetanus
Cholera (New)
Capsular polysaccharide Meningococcus
Pneumococcus
Haemophilus
Typhoid (New)
Surface antigen Hepatitis B
 ADJUVANTS

• Nonliving vaccines, especially those consisting of small molecules

require the inclusion of agents to enhance their effectiveness.
• These adjuvants include microbial, synthetic and endogenous
preparations having adjuvant activity, but at present only
aluminium or calcium salts are generally used in humans.
• Adjuvants should enable antigens to be slowly released, preserve
antigen integrity, target antigen presenting cells and induce
cytotoxic lymphocytes.
• Vaksin tidak hidup, terutama yang terdiri dari molekul
kecil membutuhkan agen untuk meningkatkan
efektivitasnya.
• Bahan pembantu ini meliputi mikroba, sediaan sintetis
dan endogen yang memiliki aktivitas bahan pembantu,
tetapi saat ini hanya garam aluminium atau kalsium yang
umumnya digunakan pada manusia.
• Adjuvan harus memungkinkan antigen dilepaskan secara
perlahan, menjaga integritas antigen, target sel penyajian
antigen dan menginduksi limfosit sitotoksik.
 TUMOR VACCINES

• Vaccination strategies against cancer are currently being

investigated.
• Vaccines containing tumor antigens such as those associated
with prostate cancer (prostate specific antigens) as well as
those associated with the breast, colon, and ovarian cancers
such as HER2 / neu offer hope for the future.
• Strategi vaksinasi terhadap kanker saat ini sedang diselidiki.
• Vaksin yang mengandung antigen tumor seperti yang terkait
dengan kanker prostat (antigen spesifik prostat) serta yang
terkait dengan kanker payudara, usus besar, dan ovarium seperti
HER2 / neu menawarkan harapan untuk masa depan.
VACCINES ON CLINICAL TRIALS

1. Malaria
2.Dengue
4. HIV
THANK YOU
HAEMOPHILLUS INFLUENZAE TYPE B (HIB)
Indications:
• Pneumonia, respiratory infection common in children < 2 years

Vaccine
• Conjugate polysaccharide b vaccine

Schedule:
• 6,10,14 weeks booster at 12-15 months

• Unvaccinated children ≥ 7 months of age- 2 doses

• Unvaccinated children ≥ 15 months of age- 1 dose
• Unvaccinated children ≥ 5 yrs- only if underlying immune disorder or
asplenia
Dose:
• 0.5 ml IM ant.lat.aspect of thigh

Contra-indictaions:
• Local pain, erythema, fever

 Immunogenicity-
• More than 95% of infants- protective antibody levels after a
primary series of two or three doses.
• Immunogenic in patients with increased risk for invasive
disease, such as sickle-cell disease, leukemia, (HIV) infection,
splenectomy.

• Recently, quadruple vaccine (DPT+Hib) and pentavalent

(DPT+Hib+HepB) available.
 PNEUMOCOCCAL VACCINE

A. Pneumococcal polysaccharide vaccine (PV23): 1977

- purified cap.polysaccharide Ag from 14 strains(14-valent)

Indication: widely licensed for use in adults and children aged >2 years
who have certain underlying medical conditions.(Sickle cell disease,
damaged spleen / spleenectomised , AIDS, disease affecting immune
system, diabetes, liver ds. chronic lung & heart disease, who is on
immunosuppresive therapy).

B .Pneumococcal conjugated vaccine (PCV7): 2000

Composition: Purified cap. Polysaccharide of 7 serotypes(PCV7) of
pneumococci (4, 9V, 14, 19F, 23F, 18C, 6B) conjugated to a non toxic
variant of diptheria toxin (CRM197)
Indication : infants and toddlers (6 weeks to 9 years)
• Dose: 0.5 ml
• Schedule – S/C or IM
• <6 months 3 doses (6, 10, 14wks)
• 7-11 months- 2 doses & booster after 1yr
• 12-23 months-2 doses
• >24mnths single dose

• Not recommended for >59 months of age

• No revaccination recommended

• Side-effects: Redness, tenderness, swelling ,fever, loss of appetite, irritability,

drowsiness
• Contraindications: Allergic reaction to 1st dose, Severely ill
• Efficacy of upto 57 % for cases of otitis media by serotypes represented in the
vaccine is reported.
 CHOLERA VACCINE:

Vaccine Killed whole-cell vaccine DUKORAL, 2004

(cholerae 01 in combination with
recombinant B-sub unit of cholera toxin)
Indications/Age Travellers , Aid workers assisting in disaster relief or refugee camps,
travelling to remote regions with limited access to medical care, risk
travellers with underlying gastrointestinal illness or immune
suppression >2yrs of age
Dose & route 2 doses orally
Schedule 1wk apart
3 weeks before departure
Side effects None
Contraindications Hypersensitivity to previous dose
Protection (85–90%) protection for 6 months after the second dose. Protection
declines rapidly in young children after 6 months, but remains as high
as 62% in adult vaccine recipients.
 CHOLERA VACCINE:

Vaccine Shanchol and mORCVAX

The closely related bivalent oral cholera
vaccines based on serogroups O1 and O139.

Indications/Age Above 1 years of age

Dose & route Orally, 2 doses

Schedule 2 liquid doses 14 days apart

Protection protective efficacy of the vaccine for all ages after 2 doses is 66%
licensed in 2009 as mORCVAX in Viet Nam and as Shanchol
in India; mORCVAX is currently intended for domestic
use in Viet Nam, whereas Shanchol will be produced
for Indian and international markets.
 Rotavirus vaccine:
Vaccine Rotarix™ vaccine(The monovalent RotaTeq™ vaccine(pentavalent
human ) 2007 bovine–human) 05-06
Indications/ Infants 2 and 4 months of age. Infants2, 4 and 6 months of age
Age
Route Orally 2 doses Orally 3 doses
Schedule 1st dose at 6wks & 2nd at 1st dose at 6-12wks and 2nd,3rd doses
16wks.Interval bet 2doses at least at an interval of 4-10wks
4wks
Side effects Mild & transient symptoms of Mild & transient symptoms of
gastrointestinal or respiratory tract gastrointestinal or respiratory tract

Contra Hypersensitivity, history of Hypersensitivity, history of

indications intussusception or intestinal intussusception or intestinal
malformations AGE febrile illness malformations AGE, febrile ill
 TYPHOID VACCINES
Indications:
1.Travelers going to endemic areas who will be staying for a
prolonged period of time,
2. Persons with intimate exposure to a documented S. typhi
carrier
3. Microbiology laboratory technologists who work frequently
with S. typhi
4.Immigrants
5. Military personnel
Two types:

1. Injectable Typhoid vaccine

(TYPHIM –Vi,TYPHIVAX)

2. The live oral vaccine (TYPHORAL)

• Injectable Typhim –Vi

1.This single-dose injectable typhoid vaccine, from the

bacterial capsule of S. typhi strain of Ty21a.
2.This vaccine is recommended for use in children over 2
years of age.
3.Sub-cutaneous or intramuscular injection
4.Efficacy : 64% -72%
Typhoral vaccine:

1. live-attenuated-bacteria vaccine manufactured from the Ty21a strain of S.

typhi.
2. The efficacy rate of the oral typhoid vaccine ranges from 50-80%
3. Not recommended for use in children younger than 6 years of age.
4. The course consists of one capsule orally, taken an hour before food with a
glass of water or milk (1stday,3rd day &5th day)
5. No antibiotic should be taken during this period
6. Immunity starts 2-3 weeks after administration and lasts for 3 years
7. A booster dose after 3 years
 HEPATITIS A
Type of vaccine Inactivated (killed)

Number of doses Two 0.5ml i.m. Second dose 6–24 months after the
first

Booster May not be necessary

Contraindications Hypersensitivity to previous dose

Adverse reactions Mild local reaction of short duration, mild systemic

reaction

Before departure Protection 2–4 weeks after first dose

Recommended All non-immune travellers to endemic areas

 COMBINED HEPATITIS A AND HEPATITIS B VACCINE

• 2001- FDA

• Twinrix (GlaxoSmithKline)

• The vaccine is administered in a three-dose series at 0, 1,

and 6 months

• Twinrix is approved for persons aged ≥18 years with

indications for both hepatitis A and hepatitis B vaccines.
 MENINGOCOCCAL VACCINE:
Indications:
• Travellers to industrialized countries are exposed to the possibility of sporadic
cases.

• Outbreaks of meningococcal C disease occur in schools, colleges, military

barracks and other places where large numbers of adolescents and young
adults congregate.

• Long-term travellers living in close contact with the indigenous population

may be at greater risk of infection.

• Vaccines: - Polysaccharide vaccine

- Conjugate vaccine
Polysaccharide vaccines:
• bivalent (A and C) or tetravalent (A, C, Y and W-135)
• One dose, provides protection for 3–5 years
• Vaccine should be given 2 weeks before departure
• Children under 2 years of age are not protected by the vaccine
• Travellers should opt (A, C, Y, W-135) than the bivalent vaccine
Conjugate vaccine:
• Monovalent serogroup C conjugate vaccines
• licensed for use since 1999
• incorporated in national vaccination programmes in an increasing number of countries.
• prolonged duration of protection in infants who are vaccinated at 2, 3 and 4 months of age.
 VARICELLA

• In several industrialized countries, Varicella vaccines have been

introduced into the childhood immunization programmes.
• Most adult travellers from temperate climates are immune (as a result of
either natural disease or immunization).
• Adult travellers without a history of Varicella who travel from tropical
countries to temperate climates may be at increased risk and should
consider vaccination.
• Use at 9 months of age and older. optimal age for Varicella vaccination is
12–24 months.
• In Japan and several other countries 1 dose of the vaccine is considered
sufficient regardless of age.
• In the United States 2 doses 4–8 weeks apart, are recommended for
adolescents and adults.
Side effects:
• Mild Varicella-like disease with rash within 4 weeks.
Contraindications
• Pregnancy (pregnancy should be avoided for 4 weeks following
vaccination),
• Ongoing severe illness
• Anaphylactic reactions
• Immuno suppression.
MMR VARICELLA VACCINE (MMRV)
 Vaccination schedule and use-
• 12 months- 12 yrs of age
• 1st dose as early as possible after 12 months of age, 2nd after at least 3 months
interval
• Post-exposure prophylaxis within 3 days

 Adverse reactions-
• Fever, measles like rash 5-12 days after vaccination, febrile seizures ( risk
higher than MMR and Varicella given separately)

 Storage-
• Very fragile, -15°C
• Never at room temp.or refrigerator
• Diluent (sterile water) - refrigerator or room temp.
 HUMAN PAPILLOMA VIRUS VACCINE
Vaccine Quadrivalent vaccine (2006) Bivalent vaccine (2007)
VLPs for 6,11,16,18 VLPs for 16,18
Indications Young adolescent girls as young as 9 years Young adolescent girls as
& prevention of anogenital warts in young as 10 years
females & males
Dose &route 0.5ml IM 0.5ml IM
Schedule 0, 2 & 6 months. minimum 4 wks interval 0, 1 & 6 months.2nd dose bet
bet 1st & 2nd &12 wks bet 2nd&3rd 1 and 2 ½ months after the
1st dose.
Side effects Mild and transient local reactions at the same
site of injection i.e erythema, pain or
swelling
Contraindicatio severe allergic reactions to previous dose, same
ns severe acute illness, pregnant females

Protection 70% against cervical cancers 70% against cervical cancers

 JAPANESE ENCEPHALITIS

Indications:

 Vaccination is recommended for travellers with extensive outdoor

exposure (camping, hiking, bicycle tours, outdoor occupational
activities, in particular in areas where flooding irrigation is practiced)

 In rural areas of an endemic region during the transmission season.

 It is also recommended for expatriates living in endemic areas through

a transmission season or longer.
JAPANESE ENCEPHALITIS VACCINES
 Currently, three types of JE vaccines in use:

1. Mouse brain-derived inactivated vaccine.

2. Cell culture-derived inactivated vaccine and
3. Cell culture-derived live attenuated vaccine.

 No JE vaccine- WHO-prequalified

 The Mouse Brain-derived Inactivated Vaccine: (MBD)

• Produced in several Asian countries including India (Central

Research Institute, Kasauli).
• So far, the only type of JE vaccine that is commercially available in the
international market.
• Safe, efficacious
• Disdvantages of the MBD vaccine

 Multiple doses ( 3 Primary + Booster)

 Expensive vaccine, complicated schedule, side effects
 Low availability
- Production stopped by major manufacturers globally
- CRI may also close down the production

 Cell-culture-derived inactivated vaccine

• Manufactured in China
• Based upon the Beijing P-3 strain
• High viral yields when propagated in primary hamster kidney
cells.
• Formalin-inactivated vaccine, inexpensive
 Cell-culture-derived live attenuated vaccine
• 1988
• Chinese vaccine based on a stable neuro-attenuated strain of
the JE virus (SA-14-14-2).
• Licensed for use in South Korea, Nepal and Sri Lanka.

 Vaccination schedule-
• 2 doses administered 12 months apart in children aged 1–2 years and a booster at 6 years
of age
• > 6 yrs- single dose

 Immunogenicity-
• Children 6-7 years- single dose & Older children- immunized
twice at intervals of one to three months: Ab - 83%–100%

• Modest reduction in both seroconversion and Ab titre when

measles vaccine co-administered with JE vaccine
• October 04, 2013, India’s first indigenously prodcued vaccine against Japanese
Ence.phalitis (JE).

• National Institute of Virology, Indian Council of Medical Research and Bharat Biotech
Ltd. jointly developed the vaccine— JENVAC-- under the public-private-partnership.
• To begin with, the programme will focus on five worst affected states— Assam, Bihar,
Tamil Nadu, Uttar Pradesh and West Bengal.

• be administered free of cost under the National Immunization Programme.

• The vaccine, developed by Bharat Biotech, will be more expensive than the Chinese
option.
• The imported vaccine costs around Rs.20 per dose while Jenvac is likely to be priced
around Rs.70 per dose.
 INFLUENZA VACCINES
 2 Types: Inactivated And Live Attenuated

Inactivated Vaccine:
 2009-2010 influenza season (25th Feb. 2009)
• Trivalent Inactivated Vaccine (TIV):
- Type A/Brisbane/59/2007 (H1N1)
- Type A/Brisbane/10/2007 (H3N2)
- Type B/Brisbane/60/2008

Indications –
 All children 6 months to 18 yrs
 > 50 yrs of age
 Long term hospital stay
 Pregnant women
 High risk e.g. aspirin therapy, chronic diseases, haemoglobinopathies,
immunosuppression, compromised resp.function
 Vaccination schedule-

Northern hemisphere- December – March

Southern hemisphere- April - September
• TIV effective if given 2-4 months before exposure
• 6 months – 9 yrs: 2 doses 1 month apart, annually
• > 9 yrs – 1 dose annually

 Dose and route of administration-

• 0.25 ml – paediatric and 0.5 ml – adults
• Intramuscular injection

 Efficacy – varies with age, health status, similarity between vaccine

strains with circulating strains
 LIVE ATTENUATED INFLUENZA VACCINE (LAIV)
• 2003- USFDA
• Same 3 strains as TIV
• Temperature sensitive, cold adapted
• Replicate effectively in the mucosa of nasopharynx
 Efficacy-
• 87 % efficacy against culture confirmed influenza
• 27 % decrease in febrile otitis media
• Can be given anytime in influenza season
 Dose and route of administration-
• 5-8 yrs- 2 doses at least 6 wks apart
• 9-49 yrs- single dose 0.5ml
• Intranasal route, half dose in each nostril
 Adverse reactions-

Local- Swelling, erythema, induration

Systemic- (not common) fever, chills, myalgia, rarely
anaphylaxis

 Contraindications - Severe allergic reaction to prior dose,

Acute moderate to severe illness

 Storage: 2 °C and 8 °C
Must not be frozen
Opened multidose vials – till expiry date
 MALARIA VACCINES
• World’s most important parasitic disease
• No vaccine currently licensed for malaria

 Challenges –
• Complex malarial parasite life cycle
• Each stage- immunologically distinct
• Perception- limited market potential

 Asexual stage vaccines-

• Based on the Ag of Pf in man
• Reduce severe complicated malaria- ↓mortality and morbidity
So, WHO research priority vaccines
e.g. Synthetic Pf (Pfs) conjugate vaccines (Pfs 66) Recombinant protein based
vacines
Sexual stage vaccines-
• Transmission blocking vaccines
• e.g. Pfs 25 conjugate vaccine

Pre-erythrocytic stage vaccines-

• Pre clinical stage
e.g. radiation attenuated sporozoite vaccines, polypeptide
DNA vaccines, circumsporozoite (CS) protein vaccines
 DENGUE VACCINES
 4 types of dengue vaccines under clinical trials:
• Live tetravalent dengue vaccine
• Intertypic Chimeric vaccine (infectious clone technology)
• Chimeric vaccine
• Recombinant DNA vaccine

 Intertypic chimeric vaccine-

• Structural genes from the DNA copy of an attenuated strain of
dengue virus is replaced by the corresponding genes of a different dengue virus
serotype

 Chimeric vaccine-
• Infectious clone technology
• Replaces the E gene of the 17D yellow fever (YF) vaccine
with the analogous gene of the vaccine-targeted flavivirus
DENGUE VACCINES: CURRENT STATUS (2008)
 HIV / AIDS VACCINES

 Challenges for vaccine development:

• Viral Genetic Diversity: HIV is not just one specific virus.
• Immune Protection: We don’t know what immune responses are needed, or how strong they
need to be.
• Neutralizing Antibody: Difficult to generate broadly neutralizing antibodies.
• Vaccine Testing: Slow process, very expensive
• Transmitted by mucosal route & infected cells
• Time consuming & costly clinical trials

 Vaccine approaches in development:

 Subunit vaccine, Recombinant vector vaccine, Vaccine combination, Peptide vaccine,

Virus-like particle vaccine (pseudovirion vaccine), Plasmid DNA vaccine (nucleic acid
vaccine), Whole-inactivated virus vaccine, Live-attenuated virus vaccine
AIDS VACCINES CURRENTLY IN CLINICAL TRIALS

• Subunit Vaccines
- Recombinant envelope protein: gp 160, gp 120
- Peptide: V3 peptide, T-B peptide

• Live vector-based vaccines

- Vaccinia envelope
- Canarypox envelope

• DNA vaccines
• Preventive vaccines
• Designed for people who are not infected with HIV
• If effective, would reduce risk of infection or viral load set point after
infection

• Therapeutic vaccines
• Designed for people who are living with HIV
• If effective, would use the body’s immune system to help control or clear
HIV in the body
 YELLOW FEVER
Type of vaccine Live, attenuated (17D viral strain)
Number of doses One priming dose of 0.5 ml (s/c or im)
Booster 10-yearly (if re-certification is needed)
Contraindications Egg allergy, immunodeficiency from medication,
disease or symptomatic HIV infection,
hypersensitivity to a previous dose, pregnancy
Adverse reactions Rarely, encephalitis or hepatic failure
Before departure International certificate of vaccination becomes
valid 10 days after vaccination
Recommended All travellers to areas with risk of yellow fever
transmission

Special precautions Not for infants under 9 months of age; restrictions

in pregnancy
HEPATITIS B
• Three doses given the first two doses are usually given 1 month
apart, with the third dose 1–12 months later
• Protection for at least 15 years and probably for life. Boosters
are not recommended.
• Because of the prolonged incubation period of hepatitis B,
some protection will be afforded to most travellers following
the second dose given before travel. The final dose should
always be given upon return.
• A rapid schedule of administration of Monovalent hepatitis B
vaccine has been given day 0, 1 month 2 months. An additional
dose is given 6-12 months after the first dose.
• A very rapid schedule of administration of hepatitis B vaccine
has been proposed day 0, 7 , 21 days. An additional dose is
given at 12 months.
HEPATITIS B
• A combination vaccine that provides protection against both
hepatitis A and hepatitis B should be considered for travellers
potentially exposed to both organisms

• This inactivated vaccine is administered as follows day 0,

1 month, 6 months.

• A rapid schedule at day 0, 1 month and 2 months, with an

additional dose at 12 months

• Very rapid schedule with administration at day 0, day 7 and

day 21 with a booster dose at 12 months
HEPATITIS A
Type of vaccine Inactivated (killed)

Number of doses Two 0.5ml i.m. Second dose 6–24 months

after the first
Booster May not be necessary
Contraindications Hypersensitivity to previous dose
Adverse reactions Mild local reaction of short duration, mild
systemic reaction
Before departure Protection 2–4 weeks after first dose
Recommended All non-immune travellers to endemic areas
 VARICELLA
• In several industrialized countries, Varicella vaccines have been
introduced into the childhood immunization programmes.
• Most adult travellers from temperate climates are immune (as a
result of either natural disease or immunization).
• Adult travellers without a history of Varicella who travel from
tropical countries to temperate climates may be at increased risk
and should consider vaccination.
• Use at 9 months of age and older. optimal age for Varicella
vaccination is 12–24 months.
• In Japan and several other countries 1 dose of the vaccine is
considered sufficient regardless of age.
• In the United States 2 doses 4–8 weeks apart, are recommended
for adolescents and adults.
VARICELLA VACCINE
Side effects:
• Mild Varicella-like disease with rash within 4 weeks.
Contraindications
• Pregnancy (pregnancy should be avoided for 4 weeks
following vaccination),
• Ongoing severe illness
• Anaphylactic reactions
• Immuno suppression.
PANDEMIC INFLUENZA A (H1N1) VACCINES:

• Pandemic influenza A (H1N1) vaccines are available for use

since September 2009
• Most of these vaccines are produced using chicken eggs, while
a few manufacturers are using cell culture technology for
vaccine production
• Health care workers worldwide should be immunized as a first
priority
PNEUMOCOCCAL VACCINE
• Pneumococcal conjugated vaccine (PCV7): 2000
-infants and toddlers (6 weeks to 9 years)
• Pneumococcal polysaccharide vaccine (PV23):
• widely licensed for use in adults and children aged >2 years
who have certain underlying medical conditions.(Sickle cell
disease, damaged spleen / spleenec-tomised , AIDS, disease
affecting immune system, diabetes, liver ds. chronic lung &
heart disease, who is on immunosuppresive therapy).
• Dose: 0.5 ml
• Schedule s/c or i.m
• <6 months 3 doses (6, 10, 14wks)
• 7-11 months- 2 doses & booster after 1yr
• 12-23 months-2 doses
• >24mnths single dose
WHOLE-ORGANISM VACCINES

• Many common vaccines used consist of

inactivated or attenuated bacterial cells
or viral particles

• Includes attenuated and inactivated

vaccines