Immunization.Immunization.

Current Trends Current Trends

2007 2007 Dr.T.V.Rao MDDr.T.V.Rao MD

ImmunizationImmunization = = VaccinationVaccination

What is a VaccineWhat is a Vaccine

A vaccine is a substance that is A vaccine is a substance that is introduced into the body to prevent introduced into the body to prevent Infection or a certain PathogenInfection or a certain Pathogen Can be used in bacterial, Viral, Can be used in bacterial, Viral,

Parasitic Infections.Parasitic Infections.

History GuidesHistory Guidesthe Futurethe Future

Edward Jenner Edward Jenner VaccinatingVaccinating

Beginning of VaccinationBeginning of Vaccination..

Vaccination ( Latin ; Vaccination ( Latin ; Vacca- Cow )Vacca- Cow )

Edward Jenner used Edward Jenner used the term the term VaccinationVaccination

Cow pox virus Cow pox virus provided immunity provided immunity in prevention of in prevention of Small poxSmall pox

Scientific Era of Scientific Era of VaccinationVaccination..

Louis Pasteur adopts the Louis Pasteur adopts the principles of principles of VaccinationVaccination

For his scientific work.For his scientific work.

Vaccination for prevention Vaccination for prevention of Rabies creates of Rabies creates awareness on awareness on Immunization with Immunization with scientific fundamentalsscientific fundamentals

Major Principles Major Principles and Methods of and Methods of

VaccinationVaccination

Biological events guide the Biological events guide the

VaccinationVaccination

Major content of Major content of Vaccines Vaccines

1.1. ToxoidsToxoids

2.2. Inactivated vaccines.Inactivated vaccines.

3.3. Attenuated vaccinesAttenuated vaccines

4.4. Subunit vaccinesSubunit vaccines

5.5. Hyper immune globulins.Hyper immune globulins.

What we have achieved What we have achieved withwith

VaccinationVaccination Cost effective method in controlling Cost effective method in controlling

the infectious diseases.the infectious diseases. Small pox - Eradicated.Small pox - Eradicated. Immunization prevents many Immunization prevents many

diseasesdiseases We have created Herd immunity in We have created Herd immunity in

commonly prevalent diseases.commonly prevalent diseases.

Eradication of Small PoxEradication of Small Pox

WHO efforts with WHO efforts with various various

Governmental and Governmental and Social Social

Organizations have Organizations 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 Different protocols to ImmunizationImmunization

Passive ImmunizationPassive Immunization

Active ImmunizationActive Immunization..

Passive ImmunizationPassive Immunization Passive immunizationPassive immunization Artificially 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 Antibodies are created in various sources from animals to humansto humans

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,

Passive ImmunizationPassive Immunization

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

Botulism - Antitoxin Botulism - Antitoxin Tetanus – Antitoxin. – Equine Tetanus – Antitoxin. – Equine

Human Tetanus Immunoglobulin,Human Tetanus Immunoglobulin,

Pooled Immunoglobulins Pooled Immunoglobulins

Human Normal Immunoglobulin Human Normal Immunoglobulin Used for short term prophylaxis,Used for short term prophylaxis, Eg Hepatitis A Immunoglobulin,Eg Hepatitis A Immunoglobulin,

Passive ImmunizationPassive ImmunizationHighly Successful Highly Successful

Saves in Acute InfectionsSaves in Acute Infections

Diphtheria AntitoxinDiphtheria Antitoxin

Tetanus AntitoxinTetanus Antitoxin

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

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

Active Active ImmunizationImmunization..

Most Ideal, Cost effective, method Most Ideal, Cost effective, method to prevent communicable to prevent communicable

Diseases.Diseases.

Active Immunization with Active Immunization with ToxoidsToxoids

Types 1Types 1

Toxoids - Single Toxin Modified Toxoids - Single Toxin Modified

Preserves Antigenicity,Preserves Antigenicity,

Loses its Toxicity.Loses its Toxicity.

Eg 1 Tetanus Toxoid Eg 1 Tetanus Toxoid

2 Diphtheria Toxoid2 Diphtheria Toxoid

Active ImmunizationActive Immunization

Inactivated / Killed Inactivated / Killed VaccinesVaccines,,

Microbes are killed Microbes are killed

Eg 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 ImmunizationActive Immunization

Attenuated Live vaccineAttenuated Live vaccine Inactivation destroys pathogen city,Inactivation destroys pathogen city,

Protective immunity is retained Protective immunity is retained

Contains living organisms with reduced Contains living organisms with reduced virulance,virulance,

1 Live polio vaccines –Sabins,1 Live polio vaccines –Sabins,

2 Yellow fever vaccine 17D strain.2 Yellow fever vaccine 17D strain.

Different Different schedules of schedules of VaccinationVaccinationMay vary from Nation to May vary from Nation to

NationNation

Depends on Geographic, Depends on Geographic, Economic and prevalence of Economic and prevalence of

Specific DiseasesSpecific Diseases

Herd ImmunityHerd Immunity Definition – When most of the People in a Definition – 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 infections Herd Immunity works in infections transmitted from person to person only.transmitted from person to person only.

The Mass oral polio vaccine creates a The Mass oral polio vaccine creates a Herd Immunity and protects the SocietyHerd Immunity and protects the Society..

Immunization Immunization SchedulesSchedules

Depend onDepend on

Need,Need,

Efficacy,Efficacy,

Safety,Safety,

Ease of administration,Ease of administration,

Vaccines which Vaccines which Changed the Changed the

History of History of MedicineMedicine

Vaccination for Polio, Tetanus Vaccination for Polio, Tetanus Diphtheria, Pertusis. Rabies Diphtheria, Pertusis. Rabies

Universally acceptedUniversally accepted

Vaccination for Diphtheria, Vaccination for Diphtheria, Tetanus and PertusisTetanus and Pertusis

Triple Antigen ( DTP )Triple Antigen ( DTP ) Contains Toxoids of Diphtheria and Contains Toxoids of Diphtheria and

Tetanus Tetanus Pertusis component Contains whole Pertusis component Contains whole

Cell preparation from Bordetella Cell preparation from Bordetella pertusis.pertusis.

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

Boosters at Later dateBoosters at Later date

Vaccination for Vaccination for PoliomyelitisPoliomyelitis

A great break through in A great break through in Vaccine ResearchVaccine Research

Millions saved from disabling Millions saved from disabling PolioPolio

Pioneers in Prevention of Pioneers in Prevention of PoliomyelitisPoliomyelitis

Vaccination in Vaccination in PoliomyelitisPoliomyelitis

Vaccination 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, A oral vaccine colonizes the gut Live attenuated vaccine, A oral vaccine colonizes the gut

produces the local immunity and antibody mediated produces the local immunity and antibody mediated immunity protects , Rarely hazardous,immunity protects , Rarely hazardous,

Salk – vaccine a killed vaccine not used in routine Salk – vaccine a killed vaccine not used in routine immunization schedules. Indiaimmunization schedules. India

Sabin’s live polio vaccine is economical for mass vaccination Sabin’s live polio vaccine is economical for mass vaccination in populous countriesin populous countries

Component of Mass Pulse Polio Immunization programmeComponent of Mass Pulse Polio Immunization programme

Commonly used Commonly used vaccines,vaccines,

MMR VaccineMMR VaccineUsed 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 months,Given at the age between 12-15 months,But Measles vaccination is done early in India at 9 But Measles vaccination is done early in India at 9

months.months.

RubellaRubella Rubella Vaccine is given separately to young Rubella Vaccine is given separately to young

womenwomen Given to all sero negative women of child bearing Given to all sero negative women of child bearing

age age

Vaccination for Vaccination for TuberculosisTuberculosis

BCG – Attenuated strains of Bovine BCG – Attenuated strains of Bovine Tubercle Bacilli, ( Bacilli –Chalmette-Tubercle Bacilli, ( Bacilli –Chalmette-Guerin)Guerin)

Efficacy ? But useful in the prevention Efficacy ? But useful in the prevention of Tuberculosis meningitis, and of Tuberculosis meningitis, and LeprosyLeprosy

Given on lateral aspect of arm, at the Given on lateral aspect of arm, at the deltoid insertion deltoid insertion

To be given intradermally,To be given intradermally,

Emerging Emerging VaccinesVaccines

Recently several persons Recently several persons benefited.benefited.

Haemophilus influenzaHaemophilus influenza Type b serotype is capsulated and highly Type b serotype is capsulated and highly

pathogenic,pathogenic, Produces Meningitis,Bacteremias, Epiglottis's.Produces Meningitis,Bacteremias, Epiglottis's. Encapsulated strain b is selected for vaccination.Encapsulated strain b is selected for vaccination. Vaccine contains capsular polysaccharide linked Vaccine contains capsular polysaccharide linked

to a protein and protects against against type B to a protein and protects against against type B strains.strains.

In U K given along with DPT vaccineIn U K given along with DPT vaccine When not given earlier A single dose for 1 – 4 When not given earlier A single dose for 1 – 4

years children.years children. Elder children and Adults do not need unless Elder children and Adults do not need unless

immunosupressed. immunosupressed.

Meningococcal VaccineMeningococcal VaccineMen C VaccineMen C Vaccine

The component of the vaccine is The component of the vaccine is Meningococcal C antigen,Meningococcal C antigen,

The polysaccharide component is The polysaccharide component is linked to protein carrier,linked to protein carrier,

In developed countries given at 2, 3, In developed countries given at 2, 3, 4 months duration.4 months duration.

Produces prolonged immune Produces prolonged immune response.response.

Vaccination in Hepatitis A Vaccination in Hepatitis A Virus Infection Virus Infection

A formaldehyde inactivated vaccine A formaldehyde inactivated vaccine prepared from HAV grown in Diploid cellsprepared from HAV grown in Diploid cells

A vaccination is effective for 10 A vaccination is effective for 10 yearsyears

Advised mainly in persons entering Advised mainly in persons entering endemic areas with HAV Infection.endemic areas with HAV Infection.

Bio-Engineering Bio-Engineering createscreates VaccineVaccine

Hepatitis B VaccineHepatitis B Vaccine

Molecular Biology and Molecular Biology and Genetic Engineering Genetic Engineering contributed for HBV contributed for HBV

VaccineVaccine..

Vaccination for Hepatitis B Vaccination for Hepatitis B InfectionInfection..

Hepatitis B VaccineHepatitis B Vaccine Bio Engineered vaccine,Bio Engineered vaccine,

0 - 1 - 6 months 0 - 1 - 6 months ( Dosage )( Dosage )

Deltoid region Deltoid region 90% successful90% successful Universal Immunization – Universal Immunization – an ideal goal an ideal goal

in prevention of Hepatitis B infectionsin prevention of Hepatitis B infections..

Combined Vaccination for Combined Vaccination for Hepatitis A and B Hepatitis A and B

Infections.Infections.

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

Available as Available as

TWINRIX ( GSK )TWINRIX ( GSK )

Vaccination for TyphoidVaccination for Typhoid Oral – Live ( Typhoral )Oral – Live ( Typhoral ) Stable mutant of S.typhiStable mutant of S.typhi Strain Ty2 ( Lacking enzyme UDP –Strain Ty2 ( Lacking enzyme UDP –

Galactose 4 Epimerase).Galactose 4 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 Needed for people traveling to Endemic areasareas

Other VaccinesOther Vaccines Pneumococcal vaccinePneumococcal vaccine A polyvalent polysaccharide containing capsular A polyvalent polysaccharide containing capsular

antigen with 23 Sero typesantigen with 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, heart,Chronic diseases of Liver, lungs, heart, Renal failure.Renal failure. HIV infection HIV infection Effective in > 2 years old children, Effective in > 2 years old children,

Vaccine for Varicella Vaccine for Varicella zosterzoster

OKA strain, A live attenuated strain,OKA strain, A live attenuated strain, Single dose for children ( 1-12 years Single dose for children ( 1-12 years

children)children) Not to be given in Immune Not to be given in Immune

suppressed / HIV patients.suppressed / HIV patients.

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

Always use new vaccines with Always use new vaccines with prevailing strains,prevailing strains,

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

Made in embroyonated eggs.Made in embroyonated eggs.

New VaccinesNew VaccinesDeveloped or on TrailsDeveloped or 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 trails in Africa, and MalawiUnder Phase III trails in Africa, and Malawi Rota Teq ( MEREK)Rota Teq ( MEREK) Introduced in NicaraguaIntroduced in Nicaragua

Newer Pneumococcal Newer Pneumococcal VaccineVaccine

A Seven Valent conjugate vaccine A Seven Valent conjugate vaccine (Prevenar )(Prevenar )

Effective against 7 strains prevalent Effective against 7 strains prevalent in certain geographic locationsin certain geographic locations

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

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

Human Papilloma Virus Human Papilloma Virus VaccineVaccine

Gardasil ( HPV vaccine ) developed by Gardasil ( HPV vaccine ) developed by Merck.Merck.

Effective against 4 common serotypesEffective against 4 common serotypes

( includes prominent serotypes 16 and ( includes prominent serotypes 16 and 18 causing Cancer cervix ).18 causing Cancer cervix ).

Adolescents and preadolescents Adolescents and preadolescents considered for vaccination.considered for vaccination.

Newer Meningococcal Newer Meningococcal Meningitis A Vaccine ( Men Meningitis A Vaccine ( Men

A )A )

Effective in Meningococcal Diseases Effective in Meningococcal Diseases

Phase I trails in IndiaPhase I trails in India

Phase II trails , Mali, and GambiaPhase II trails , Mali, and Gambia

Phase III trails in Ethiopia /SenegalPhase III trails in Ethiopia /Senegal

Influenza Influenza Current VaccineCurrent Vaccine

In view of changing strains the In view of changing strains the

antigens configuration for Influenza antigens configuration for Influenza need a new model vaccine every year / need a new model vaccine every year / frequentlyfrequently

Currently CSL Biotherapies vaccine is Currently CSL Biotherapies vaccine is licensed on 28licensed on 28thth Sept 2007 for current Sept 2007 for current use.use.

Need for Vaccines in HIV/AIDS

Why Vaccines are Difficult to Why Vaccines are Difficult to Development in AIDSDevelopment in AIDS

H I V infection is produced by most H I V infection is produced by most complex virus ever identified and it is complex virus ever identified and it is extremely good at evading any Immune extremely good at evading any Immune Mediated strategy detected against.Mediated strategy detected against.

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

New forms ( clades ) are emerging all New forms ( clades ) are emerging all through infection,through infection,

Vaccine OptionsVaccine Options

1 Live attenuated or whole killed HIV 1 Live attenuated or whole killed HIV virus virus Failed due to safety fears, Failed due to safety fears, Trails stoppedTrails stopped..

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

Failed in Major trailsFailed in Major trails..

3 DNA vaccines 3 DNA vaccines

Isolated HIV genes used to stimulate Isolated HIV genes used to stimulate

cell mediated Immunitycell mediated Immunity..

Vaccine Options ( Contd )Vaccine Options ( Contd )

4 Recombinant Vaccine - Isolated 4 Recombinant Vaccine - Isolated genes delivered through another viral genes delivered through another viral vector,vector,

Most trials use this methodMost trials use this method

Vaccine OptionsVaccine Options

5 Combination Vaccines.5 Combination Vaccines.

Multiples trails are in progress Multiples trails are in progress with combination of Designs, with combination of Designs, strategies, strategies,

And And

Immunogens which can produce a Immunogens which can produce a broader more powerful, and more broader more powerful, and more durable immune response.durable immune response.

The Quest for the The Quest for the AIDS vaccine AIDS vaccine

continuescontinues

Various National and International Various National and International Organization are committed for Organization are committed for

development of a effective development of a effective VaccineVaccine

Present HIV Vaccination Present HIV Vaccination TrailsTrails

Vaccination for Vaccination for People at special riskPeople at special risk

AnthraxAnthrax CholeraCholera Hepatitis AHepatitis A Hepatitis BHepatitis B InfluenzaInfluenza Japanese B Japanese B

encephalitisencephalitis Meningococcal Meningococcal

InfectionInfection PlaguePlague

Pneumococcal Pneumococcal infectioninfection

Q fever,Q fever, Rabies Rabies Tick borne Tick borne

encephalitis.encephalitis. TyphoidTyphoid Typhus Typhus Varicella ZosterVaricella Zoster Yellow fever.Yellow fever.

Contraindication to Contraindication to VaccinationVaccination

In spite of great success with In spite of great success with many vaccines, yet a caution many vaccines, yet a caution

and wisdom are essentialand wisdom are essential

II

Contra -indications to Contra -indications to VaccinationVaccination

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

Avoid giving live vaccines to pregnant Avoid giving live vaccines to pregnant womenwomen

Avoid all types of vaccines in the first Avoid all types of vaccines in the first Trimester of pregnancy,Trimester of pregnancy,

Do not give live vaccines to Do not give live vaccines to immunosupressed patients and patients immunosupressed patients and patients suffering with RES malignancies,suffering with RES malignancies,

Contraindication ( Cont )Contraindication ( Cont )

In spite of Immune suppression in In spite of Immune suppression in HIV infected, we can still give MMR HIV infected, we can still give MMR and Oral polio drops ( But Salk killed and Oral polio drops ( But Salk killed vaccine is safe).vaccine is safe).

In HIV patients do not give BCG In HIV patients do not give BCG vaccinevaccine

What is an ideal What is an ideal vaccine.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 Yet there is No Ideal VaccineVaccine..

Care in VaccinationCare in Vaccination Some subjects may develop acute Some subjects may develop acute

anaphylaxis with vaccination,anaphylaxis with vaccination, Be prepared to resuscitate the Be prepared to resuscitate the

individuals,individuals,

Unresolved Unresolved problemsproblems

Nothing is perfectNothing is perfect No Vaccine is totally ProtectiveNo Vaccine is totally Protective Influenza – Needs very frequent Influenza – Needs very frequent

updating updating Cholera vaccine –Little effective in Cholera vaccine –Little effective in

realityreality

WHOWHO InitiativesInitiatives

On Vaccine Strategies On Vaccine Strategies and Developmentand Development

WHOWHO

Supports the Research of various Biological Supports the Research of various Biological Organizations which produce the Newer Organizations which produce the Newer VaccinesVaccines

Helps the Implementation Helps the Implementation various programmers various programmers

related to Vaccinesrelated to Vaccines

Vaccine ResearchVaccine Research

Now major research is focused on finding Now major research is focused on finding the safe and Socially acceptable vaccinesthe safe and Socially acceptable vaccines

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

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

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

Science Hopes a Vaccine Science Hopes a Vaccine for every Diseasefor every Disease

Vaccination created HOPE in Vaccination created HOPE in HumanityHumanity

Created for Created for awareness among awareness among Medical and Health Medical and Health

care workers in care workers in Developing world.Developing world.

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

tvraodoctor2000@yahoo.co.intvraodoctor2000@yahoo.co.in