Immunization Dr T V Rao

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ImmunizationImmunization

Current TrendsCurrent Trends

2008 2008

Dr.T.V.Rao MDDr.T.V.Rao MD



ImmunizationImmunization == VaccinationVaccination

What is a VaccineWhat is a Vaccine

A vaccine is a substance that isA vaccine is a substance that isintroduced into the body to preventintroduced into the body to preventInfection by a certain PathogenInfection by a certain Pathogen

Can be used in bacterial, Viral,Can be used in bacterial, Viral,Parasitic Infections.Parasitic Infections.



History GuidesHis

tory Guides

the Futurethe Future



Edward Jenner Vaccinating Edward Jenner Vaccina

ting



Beginning of VaccinationBeginning of Vaccination..

Vaccination ( Latin ;Vaccination ( Latin ;

Vacca- Cow )Vacca- Cow )

Edward Jenner usedEdward Jenner used

the term Vaccinationthe term Vaccination

Cow pox virusCow pox virus

provided immunity inprovided immunity inprevention of Smallprevention of Small

poxpox



Scientific Era of VaccinationScientific Era of Vaccination..

Louis Pasteur adopts theLouis Pasteur adopts the

principles of Vaccinationprinciples of VaccinationFor his scientific work.For his scientific work.

Vaccination for preventionVaccination for prevention

of Rabies createsof Rabies createsawareness onawareness on

Immunization withImmunization with

scientific fundamentalsscientific fundamentals



Major Principles and Ma jor Principles and

Methods of VaccinationMethods of Vaccination

Biological events guide theBiological events guide the

VaccinationVaccination



Major content of VaccinesM ajor content of Vaccines

ToxoidsToxoids

Inactivated vaccines.Inactivated vaccines. Attenuated vaccinesAttenuated vaccines

Subunit vaccinesSubunit vaccines

Hyper immune globulins.Hyper immune globulins.

Wh t h hi d ithWh t h hi d ith



What we have achieved withWhat we have achieved with


Cost effective method in controlling theCost effective method in controlling the

infectious diseases.infectious diseases.

Small pox - Eradicated.Small pox - Eradicated.

Immunization prevents many diseasesImmunization prevents many diseases

We have created Herd immunity inWe have created Herd immunity in

commonly prevalent diseases.commonly prevalent diseases.



Eradication of Small PoxEradication of Small Pox

WHO efforts withWHO efforts withvarious Governmentalvarious Governmental

and Socialand Social

Organizations haveOrganizations have

changed History of changed History of MedicineMedicine



Principles of Immunization

Development of Immunology Development of Immunology

has foundations on Vaccineshas foundations on Vaccines



Different protocols to ImmunizationDifferent protocols to Immunization

Passive ImmunizationPassive Immunization

Active ImmunizationActive Immunization..




Passive immunizationPassive immunizationArtificially created by passive methodArtificially created by passive method

Can be created at short notice,Can be created at short notice,

Effective for limited periods,Effective for limited periods,

Antibodies are created in various sources from animals toAntibodies are created in various sources from animals tohumanshumans

Can be Antiviral ,Antibacterial,Can be Antiviral ,Antibacterial,Source can be Animals, or HumansSource can be Animals, or Humans

Human source will be effective for 3-6 months.Human source will be effective for 3-6 months.

Animals ( Heterologus ) effective for few weeks,Animals ( Heterologus ) effective for few weeks,




Diphtheria antitoxin - Horse- Equine Diptheriae antitoxin.Diphtheria antitoxin - Horse- Equine Diptheriae antitoxin.

Botulism - AntitoxinBotulism - Antitoxin

Tetanus – Antitoxin. – EquineTetanus – Antitoxin. – Equine

Human Tetanus ImmunoglobulinHuman Tetanus Immunoglobulin

Pooled ImmunoglobulinsPooled Immunoglobulins

Human Normal ImmunoglobulinHuman Normal Immunoglobulin

Used for short term prophylaxis,Used for short term prophylaxis,

Eg Hepatitis A Immunoglobulin,Eg Hepatitis A Immunoglobulin,

P i I i iP i I i ti




Highly SuccessfulHighly Successful

Saves in Acute InfectionsSaves in Acute Infections

Diphtheria AntitoxinDiphtheria AntitoxinTetanus AntitoxinTetanus Antitoxin

Rabies Hyper immune Globulins( HRIG )Rabies Hyper immune Globulins( HRIG )

Varicella Zoster Hyper Immune GlobulinsVaricella Zoster Hyper Immune Globulins(HZIG)(HZIG)



Active Immunization Active Immunization..

Most Ideal, Cost effective, methodMost Ideal, Cost effective, methodto prevent communicableto prevent communicable

Diseases.Diseases.



Active Immunization with ToxoidsActive Immunization with Toxoids

Types 1Types 1

Toxoids - Single Toxin ModifiedToxoids - Single Toxin Modified

Preserves Antigenicity,Preserves Antigenicity,Loses its Toxicity.Loses its Toxicity.

Eg 1. Tetanus ToxoidEg 1. Tetanus Toxoid

2. Diphtheria Toxoid2. Diphtheria Toxoid



Active Immunization Active Immunization

Inactivated / Killed VaccinesInactivated / Killed Vaccines,,

Microbes are killedMicrobes are killedEg 1 Pertusis (Whooping cough )Eg 1 Pertusis (Whooping cough )

2 Influenza ( Flu)2 Influenza ( Flu)

3 Salk - Killed vaccine for 3 Salk - Killed vaccine for

(Poliomyelitis)(Poliomyelitis)



Active Immunization Active Immunization

Attenuated Live vaccineAttenuated Live vaccine

Inactivation destroys pathogenicity,Inactivation destroys pathogenicity,

Protective immunity is retainedProtective immunity is retainedContains living organisms with reducedContains living organisms with reduced

virulencevirulence

1 Live polio vaccines –Sabin's1 Live polio vaccines –Sabin's2 Yellow fever vaccine 17D strain.2 Yellow fever vaccine 17D strain.



Different schedules of Different schedules of

VaccinationVaccinationMay vary from Nation toMay vary from Nation to

NationNationDepends on Geographic,Depends on Geographic,

Economic and prevalence of Economic and prevalence of

Specific DiseasesSpecific Diseases





Herd Immunity Herd Immunity

Definition – When most of the People in aDefinition – When most of the People in a

community are immune to particular community are immune to particular

infection-Natural transmission is inhibited.infection-Natural transmission is inhibited.

Herd Immunity works in infectionsHerd Immunity works in infections

transmitted from person to person only.transmitted from person to person only.

The Mass oral polio vaccine creates aThe Mass oral polio vaccine creates a

Herd Immunity and protects the SocietyHerd Immunity and protects the Society..



Immunization SchedulesImmunization Schedules

Depend onDepend on

Need,Need,

Efficacy,Efficacy,

Safety,Safety,

Ease of administration,Ease of administration,



Vaccines whichVaccines whichChanged the History of Changed the History of

MedicineMedicineVaccination for Polio, TetanusVaccination for Polio, Tetanus

Diphtheria, Pertusis. RabiesDiphtheria, Pertusis. RabiesUniversally acceptedUniversally accepted



Vaccination for Diphtheria,Vaccination for Diphtheria,

Tetanus and PertusisTetanus and Pertusis

Triple Antigen ( DTP )Triple Antigen ( DTP )

Contains Toxoids of Diphtheria andContains Toxoids of Diphtheria andTetanusTetanus

Pertussis component Contains wholePertussis component Contains wholeCell preparation from BordetellaCell preparation from Bordetellapertussis.pertussis.

Three Doses given at the interval of 4-6Three Doses given at the interval of 4-6weeksweeks

Boosters at Later dateBoosters at Later date



Vaccination for Vaccination for

PoliomyelitisPoliomyelitis

A great break through inA great break through in

Vaccine ResearchVaccine ResearchMillions saved from disablingMillions saved from disabling

PolioPolio



Pioneers in Prevention of Pioneers in Prevention of

PoliomyelitisPoliomyelitis



Vaccination inVaccination in

PoliomyelitisPoliomyelitisVaccination for Poliomyelitis, can be oral or inject able.Vaccination for Poliomyelitis, can be oral or inject able.

Sabins – Mixture of 3 types poliovirus1,2,3Sabins – Mixture of 3 types poliovirus1,2,3

Live attenuated vaccine, oral vaccine colonizes the gutLive attenuated vaccine, oral vaccine colonizes the gutproduces the local immunity and antibody mediated immunityproduces the local immunity and antibody mediated immunity

protects , Rarely hazardous.protects , Rarely hazardous.

Salk – killed vaccine not used in routine immunization schedules inSalk – killed vaccine not used in routine immunization schedules inIndiaIndia

Sabin’s live polio vaccine is economical for mass vaccination inSabin’s live polio vaccine is economical for mass vaccination in

populous countriespopulous countries

Component of Mass Pulse Polio Immunization programs.Component of Mass Pulse Polio Immunization programs.



Commonly used vaccinesCommonl y used vaccines

MMR VaccineMMR Vaccine

Used for the prevention of Used for the prevention of

Measles, Mumps, and Rubella.Measles, Mumps, and Rubella.

Contains live attenuated strains,Contains live attenuated strains,Given at the age between 12-15 monthsGiven at the age between 12-15 months

But Measles vaccination is done early in India at 9 months.But Measles vaccination is done early in India at 9 months.

RubellaRubellaRubella Vaccine is given separately to young womenRubella Vaccine is given separately to young women

Given to all sero negative women of child bearing ageGiven to all sero negative women of child bearing age



Vaccination for TuberculosisVaccination for Tuberculosis

BCG – Attenuated strains of BovineBCG – Attenuated strains of Bovine

Tubercle Bacilli, ( Bacilli –Calmette-Tubercle Bacilli, ( Bacilli –Calmette-

Guerin)Guerin)

Efficacy ? But useful in the prevention of Efficacy ? But useful in the prevention of

Tuberculosis meningitis, and LeprosyTuberculosis meningitis, and Leprosy

Given on lateral aspect of arm, at theGiven on lateral aspect of arm, at the

deltoid insertiondeltoid insertion

To be given intradermallyTo be given intradermally



Emerging VaccinesEmerging Vaccines

Recently several personsRecently several personsbenefited.benefited.



Haemophilus influenzaHaemophilus influenza

Type b serotype is capsulated and highlyType b serotype is capsulated and highlypathogenic,pathogenic,

Produces Meningitis,Bacteremias, Epiglottis.Produces Meningitis,Bacteremias, Epiglottis.

Encapsulated strain b is selected for vaccination.Encapsulated strain b is selected for vaccination.

Vaccine contains capsular polysaccharide linkedVaccine contains capsular polysaccharide linkedto a protein and protects against type B strains.to a protein and protects against type B strains.

In UK given along with DPT vaccineIn UK given along with DPT vaccine

When not given earlier A single dose for 1 – 4When not given earlier A single dose for 1 – 4years children.years children.Elder children and Adults do not need unlessElder children and Adults do not need unlessimmunosupressed.immunosupressed.



Meningococcal VaccineMeningococcal Vaccine

Men C VaccineMen C Vaccine

The component of the vaccine isThe component of the vaccine is

Meningococcal C antigen,Meningococcal C antigen,

The polysaccharide component is linked toThe polysaccharide component is linked to

protein carrier,protein carrier,

In developed countries given at 2, 3, 4In developed countries given at 2, 3, 4

months duration.months duration.

Produces prolonged immune response.Produces prolonged immune response.



Vaccination in Hepatitis AVaccination in H epatitis A

Virus InfectionVirus Infection

A formaldehyde inactivated vaccineA formaldehyde inactivated vaccine

prepared from HAV grown in Diploid cellsprepared from HAV grown in Diploid cells

vaccination is effective for 10 yearsvaccination is effective for 10 years

Advised mainly in persons enteringAdvised mainly in persons enteringendemic areas with HAV Infection.endemic areas with HAV Infection.



Bio-Engineering createsBio-Engineering creates

VaccineVaccine

Hepatitis B VaccineHepatitis B Vaccine

Molecular Biology and GeneticMolecular Biolo

gy and Genetic



Molecular Biology and Genetic Molecular Biology and Genetic

Engineering contributed for HBV Engineering contributed for HBV

VaccineVaccine..



Vaccination for Hepatitis BVaccination for Hepatitis B

InfectionInfection..

Hepatitis B VaccineHepatitis B Vaccine

Bio Engineered vaccine,Bio Engineered vaccine,

0 - 1 - 6 months ( Dosage )0 - 1 - 6 months ( Dosage )Deltoid regionDeltoid region

90% successful90% successful

Universal Immunization –Universal Immunization – an ideal goal inan ideal goal inprevention of Hepatitis B infectionsprevention of Hepatitis B infections..



Combined Vaccination for Combined Vaccination for

Hepatitis A and B Infections.H epatitis A and B Infections.

Now a combined vaccine is available for Now a combined vaccine is available for prevention of Hepatitis A and Bprevention of Hepatitis A and B

Available asAvailable as

TWINRIX ( GSK )TWINRIX ( GSK )



Vaccination for Typhoid Vaccination for T yphoid

Oral – Live ( Typhoral )Oral – Live ( Typhoral )

Stable mutant of S.typhiStable mutant of S.typhi

Strain Ty2 ( Lacking enzyme UDP –GalactoseStrain Ty2 ( Lacking enzyme UDP –Galactose44 Epimerase).Epimerase).

Injectable vaccine ( Ty vi ) containsInjectable vaccine ( Ty vi ) contains

Purified Vi polysaccharide AntigenPurified Vi polysaccharide Antigen

Efficacy lasts for 3 yearsEfficacy lasts for 3 years

Needed for people traveling to Endemic areasNeeded for people traveling to Endemic areas



Other VaccinesOther Vaccines

Pneumococcal vaccinePneumococcal vaccineA polyvalent polysaccharide containing capsular antigenA polyvalent polysaccharide containing capsular antigenwith 23 Sero typeswith 23 Sero types

Gives 80 -90 % protectionGives 80 -90 % protection

Used inUsed in

Dysfunctional spleenDysfunctional spleen

Sickle cell diseases,Sickle cell diseases,

Chronic diseases of Liver, lungs, heartChronic diseases of Liver, lungs, heart

Renal failure.Renal failure.

HIV infectionHIV infection

Effective in > 2 years old childrenEffective in > 2 years old children



Vaccine for Varicella zoster Vaccine for Varicella zoster

OKA strain, A live attenuated strain,OKA strain, A live attenuated strain,

Single dose for children ( 1-12 yearsSingle dose for children ( 1-12 years

children)children)

Not to be given in Immunosuppressed /Not to be given in Immunosuppressed /

HIV patients.HIV patients.



Vaccine for Influenza(virus )Vaccine for Influenza(virus )

Always use new vaccines with prevailingAlways use new vaccines with prevailing

strainsstrains

Now recombinant vaccines are available.Now recombinant vaccines are available.

Made in embroyonated eggs.Made in embroyonated eggs.



New VaccinesNew Vaccines

Developed / on TrailsDeveloped / on Trails



Vaccines for Rota VirusVaccines for Rota Virus

Rota Rix ( GSK )Rota Rix ( GSK )

Introduced in Brazil, Elsalvador, Mexico,Introduced in Brazil, Elsalvador, Mexico,Panama and VenezuelaPanama and Venezuela

Under Phase III trials in Africa, and MalawiUnder Phase III trials in Africa, and Malawi

Rota Teq ( MEREK)Rota Teq ( MEREK)

Introduced in NicaraguaIntroduced in Nicaragua



Newer Pneumococcal VaccineNewer Pneumococcal Vaccine

A Seven Valent conjugate vaccineA Seven Valent conjugate vaccine

(Prevenar )(Prevenar )

Effective against 7 strains prevalent inEffective against 7 strains prevalent in

certain geographic locationscertain geographic locations

Effective in 83 % HIV uninfected.Effective in 83 % HIV uninfected.

Effective in 65 % of HIV infected.Effective in 65 % of HIV infected.

H P ill ViH P

ill Vi



Human Papilloma VirusHuman P apilloma Virus

VaccineVaccine

Gardasil ( HPV vaccine ) developed byGardasil ( HPV vaccine ) developed by

Merck.Merck.

Effective against 4 common serotypesEffective against 4 common serotypes

( includes prominent serotypes 16 and 18( includes prominent serotypes 16 and 18

causing Cancer cervix ).causing Cancer cervix ).

Adolescents and preadolescentsAdolescents and preadolescents

considered for vaccination.considered for vaccination.



Newer Meningococcal MeningitisNewer Meningococcal Meningitis

A Vaccine ( Men A ) A Vaccine ( Men A )

Effective in Meningococcal DiseasesEffective in Meningococcal Diseases

Phase I trials in IndiaPhase I trials in India

Phase II trials , Mali, and GambiaPhase II trials , Mali, and Gambia

Phase III trials in Ethiopia /SenegalPhase III trials in Ethiopia /Senegal

I fl



InfluenzaInfluenza

Current VaccineCurrent Vaccine

In view of changing strains theIn view of changing strains theantigens configuration for Influenza need aantigens configuration for Influenza need a

new model vaccine every year /new model vaccine every year /frequentlyfrequently

Currently CSL Biotherapies vaccine isCurrently CSL Biotherapies vaccine islicensed on 28licensed on 28thth Sept 2007 for currentSept 2007 for currentuse.use.



Need for Vaccines in

HIV/AIDS

Wh V i Diffi lWh V i Diffi lt t



Why Vaccines are Difficult toWhy Vaccines are Difficult to

Development in AIDSDevelopment in AIDS

H I V infection is produced by most complexH I V infection is produced by most complexvirus ever identified and it is extremely good atvirus ever identified and it is extremely good at

evading any Immune Mediated strategy detectedevading any Immune Mediated strategy detectedagainst.against.

H I V is Genetically diverse.H I V is Genetically diverse.

New forms ( clades ) are emerging all throughNew forms ( clades ) are emerging all throughinfection,infection,



Vaccine OptionsVaccine Options

1 Live attenuated or whole killed HIV virus1 Live attenuated or whole killed HIV virus

Failed due to safety fears, Trials stoppedFailed due to safety fears, Trials stopped..

2 Sub Unit vaccines ( gp 20 model )2 Sub Unit vaccines ( gp 20 model )

Failed in Major trialsFailed in Major trials..

3 DNA vaccines3 DNA vaccines

Isolated HIV genes used to stimulateIsolated HIV genes used to stimulatecell mediated Immunitycell mediated Immunity..



Vaccine Options ( Contd )V accine Options ( Contd )

4. Recombinant Vaccine - Isolated genes4. Recombinant Vaccine - Isolated genesdelivered through another viral vector delivered through another viral vector

Most trials use this methodMost trials use this method



Vaccine OptionsVaccine O ptions

5 Combination Vaccines.5 Combination Vaccines.

Multiple trials are in progressMultiple trials are in progresswith combination of Designs, strategies,with combination of Designs, strategies,

AndAnd

Immunogens which can produce aImmunogens which can produce abroader more powerful, and more durablebroader more powerful, and more durable

immune response.immune response.



The Quest for the AIDS The Quest for the AIDS

vaccine continuesvaccine continues

Various National and InternationalVarious National and International

Organization are committed for Organization are committed for development of an effective Vaccinedevelopment of an effective Vaccine



Present HIV Vaccination TrialsPresent HIV Vaccination Trials

V i ti fVaccination for



Vaccination for Vaccination for

People at special risk P eople at special risk AnthraxAnthrax

CholeraCholera

Hepatitis AHepatitis A

Hepatitis BHepatitis B

InfluenzaInfluenza

Japanese BJapanese B

encephalitisencephalitisMeningococcalMeningococcal

InfectionInfection

PlaguePlague

PneumococcalPneumococcal

infectioninfection

Q fever,Q fever,

RabiesRabiesTick borneTick borne

encephalitis.encephalitis.

TyphoidTyphoidTyphusTyphus

Varicella Zoster Varicella Zoster

Yellow fever.Yellow fever.



Contraindication toContraindication to


In spite of great success withIn spite of great success with

many vaccines, yet a cautionmany vaccines, yet a cautionand wisdom are essentialand wisdom are essential

II

C t i di ti tContra indications to



Contra -indications toContra -indications to


Do not give vaccines to acutely ill patients.Do not give vaccines to acutely ill patients.

Avoid giving live vaccines to pregnantAvoid giving live vaccines to pregnant

womenwomen

Avoid all types of vaccines in the firstAvoid all types of vaccines in the first

Trimester of pregnancyTrimester of pregnancy

Do not give live vaccines toDo not give live vaccines to

immunosupressed patients and patientsimmunosupressed patients and patients

suffering with RES malignanciessuffering with RES malignancies



Contraindication ( Cont )Contraindic ation ( Cont )

In spite of Immune suppression in HIVIn spite of Immune suppression in HIV

infected, we can still give MMR and Oralinfected, we can still give MMR and Oral

polio drops ( But Salk killed vaccine ispolio drops ( But Salk killed vaccine is

safe).safe).

In HIV patients do not give BCG vaccineIn HIV patients do not give BCG vaccine



What is an ideal vaccine.What is an ideal vaccine.

Promotes effective immunity.Promotes effective immunity.

Controls lifelong protection.Controls lifelong protection.

Safe, do not carry side effects.Safe, do not carry side effects.

Stable, cheap,Stable, cheap,

Acceptance by public.Acceptance by public.

Yet there is No Ideal VaccineYet there is No Ideal Vaccine..



Care in VaccinationCare in Vaccination

Some subjects may develop acuteSome subjects may develop acute

anaphylaxis with vaccinationanaphylaxis with vaccination

Be prepared to resuscitate the individualsBe prepared to resuscitate the individuals



Unresolved problemsUnresolved problems

Nothing is perfectNothing is perfect

No Vaccine is totally ProtectiveNo Vaccine is totally Protective

Influenza – Needs very frequent updatingInfluenza – Needs very frequent updating

Cholera vaccine –Little effective in realityCholera vaccine –Little effective in reality



WHOWHO InitiativesInitiatives

On Vaccine StrategiesOn Vaccine Strategies

and Developmentand Development



WHO WHO

Supports the Research of various BiologicalSupports the Research of various Biological

Organizations which produce the Newer Organizations which produce the Newer

VaccinesVaccines

Helps the Implementation of variousHelps the Implementation of variousprograms related to Vaccinesprograms related to Vaccines



Vaccine ResearchVaccine Research

Now major research is focused on finding theNow major research is focused on finding the

safe and Socially acceptable vaccinessafe and Socially acceptable vaccines

Refer for current knowledge on Vaccines.Refer for current knowledge on Vaccines.

VACCINEVACCINE - is a International peer-reviewed- is a International peer-reviewed journal of Vaccination Research journal of Vaccination Research

Indexed in Medline pISSN: 0264-410XIndexed in Medline pISSN: 0264-410X

Science Hopes a Vaccine forScie

nce Hopes a Vaccine for



Science Hopes a Vaccine for Science Hopes a Vaccine for

every Diseaseevery Disease

Vaccination created HOPE inVaccination created HOPE in



Vaccination created HOPE inVaccination created HOPE in

HumanityHumanity



Created for awareness amongCreated for awareness among

Medical and Health careMedical and Health care

workers in Developing world.workers in Developing world.

Dr.T.V.Rao MDDr.T.V.Rao MD

[email protected]@gmail.com

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Immunization Dr T V Rao