Bacterial Vaccine

8/10/2019 Bacterial Vaccine

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BACTERIAL VACCINES

DR. BIMAL KUMAR DAS, M.D.

DEPARETMENT OF MICROBIOLOGY ALL INDIA INSTITUTE OF MEDICAL SCIENCESNEW DELHI


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BACTERIAL VACCINES


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History and Achievementsof Vaccines

During the 15th century , an early form of smallpox vaccination waspracticed in China and other parts of the world. Healthy people wereintentionally infected with substances from the pustules of people sufferingfrom smallpox, a technique called variolation . A mild form of smallpox

usually resulted from this practice.

An English doctor, Edward Jenner , improved the variolation technique tocreate the first vaccine in 1796. Dr. Jenner had heard that dairymaids whohad been infected with cowpox, a disease related to but milder than

smallpox, were not susceptible to smallpox, and decided to test the idea.He performed the first vaccinationon a boy with material taken from lesions of cowpox. In fact, the wordvaccination comes from the Latin word for cow, vacca.


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Benefits of Vaccines Smallpox eradicated

In 1900 - >20,000 cases and 1,000 deaths

Polio eliminated

Control or near elimination of Measles Mumps Rubella Tetanus Diphtheria Pertussis Haemophilus influenzae type b (Hib)


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Vaccine PreventableBacterial Diseases

Diphtheria Pneumococcal disease

Hib disease

Meningococcal meningitisPertussis (Whooping Cough)

Tetanus (Lockjaw) Typhoid

Cholera AnthraxPlague
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Terms

Vaccination & Vaccine

Derive from the term vaccinia, the virus once used assmallpox vaccine. Originally, the term vaccine only meant

protection from smallpox.

Immunization

The process of inducing or providing immunity artificially by

administering an immunobiologic. May be passive or active


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Vocabulary Terms

Immunobiologic Antigenic substances (vaccines and toxoids) or antibody-c

Vaccine Toxoid Immune globulin (IG) Intravenous immune globulin (IGIV) Specific immune globulin Antitoxin


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How Vaccines Work

1. Active Immunization

2. Passive Immunization

3. Community immunity or herd immunity is an important part ofprotecting the community against disease


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Principles of Vaccination

General RuleThe more similar a vaccine is to

the natural disease, the better theimmune response to the vaccine.


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Immunity

Active Immunization Production of

antibody (humoralimmune response)through theadministration of avaccine or toxoid.

PassiveImmunization Provision of

temporary immunityby theadministration ofpreformedantibodies

Pooled human IG or IGIV Specific immune globulin

preparations

antitoxins


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Active

Immunity from person's own immune system. Generally long-

lasting, even a lifetime Protection after disease--immunologic memory. Memory B-cellscirculate in blood and reside in bone marrow

Vaccine

Factors that influence immune response tovaccination

Presence of maternal antibody.Nature and dose of antigen.Route of administrationPresence of adjuvants (aluminum containing materials to

improve immunogenicity, also gold).


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Properties of an ideal vaccine

1. 100% safe2. Do not cause disease in others3. No residual pathogenicity4. Will prevent disease5. Effective against all strains6. Only one dose required7. Compatibility with other vaccines8. Deliverable without hypodermic syringe9. Indefinite room temperature storage10. Cheap to manufacture11. Capable of inducing effective herd immunity


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There are two general categories of vaccines

whole-cell vaccines subunit vaccines
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Whole-cell vaccines

Whole-cell vaccines consist of entire organisms that have been modified in

some manner so that they are unable (or drastically less able) to causedisease.

Whole-agent vaccines consist of two general categories:

inactivated (whole killed)genetically attenuated (live-attenuated)

Subunit vaccines Vaccines made from well defined components of microorganisms are

called a subunit vaccine

Recombinant vaccines A subunit vaccine that is produced using recombinant techniques is

called a recombinant vaccine .
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Newer vaccines Still Experimental

DNA vaccine

Peptide vaccine

Anti-idiotype vaccine


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Advantages of DNA vaccines

1) Plasmids are easily manufactured in large amounts

2) DNA is very stable

3) DNA resists temperature extremes so storage and transport are straight forward

4) DNA sequence can be changed easily in the laboratory.

5) By using the plasmid in the vaccinee to code for antigen synthesis,

6) Mixtures of plasmids could be used that encode many protein fragments from avirus/viruses so that a broad spectrum vaccine could be produced

7) The plasmid does not replicate and encodes only the proteins of interest

8) There is no protein component and so there will be no immune response againstthe vector itself

9) there is a CTL response


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Possible Problems

1) Potential integration of plasmid into host genome leading toinsertional mutagenesis

2) Induction of autoimmune responses (e.g. pathogenic anti-DNAantibodies)

3) Induction of immunologic tolerance (e.g. where the expressionof the antigen in the host may lead to specific non-responsiveness to that antigen)


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Immunogiologic components

Suspending fluids Sterile water, saline, or fluids

containing proteins

Preservatives, stabilizers,antibiotics Inhibit or prevent bacterial

growth in viral cultures, or to

stabilize the antigens orantibodies Allergic reactions can occur if

the recipient is sensitive to oneof these additives

Thimerosal, phenol, albumin,glycine, neomycin

Adjuvants Components used

to enhance the

immunogenicity ofthe immunogiologic

Aluminumphosphate,aluminum hydroxide


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Contraindications and Precautions

Condition Live InactivatedAllergy to Component C CEncephalopathy -- CPregnancy C V

Immunosuppression C VModerate/severe illness P P

Recent Blood Product P V

C=contraindication P=precaution V=vaccinate if indicated


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Haem op hi lus inf luenzae type bVaccine

Routine ScheduleVaccine 2 mo 4 mo 6 mo 12-18 mo

HbOC x x x xPRP-T x x x x

PRP-OMP x x x

PRP-D >15 mo


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PCV7

Pneumococcal conjugate

Prevents pneumococcal disease, including bacterialmeningitis & otitis media

Vaccine effectiveness lasts 3 years

Most pneumococcal disease occurs in 1 st 2 years Recommended as of 7/21/2000 for routine use in

infants under 23 months, and high-risk infants between24-59 months

Vaccine Protective Efficacy 90%


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PCV7

Given at 2,4,6, and 12-15 months Administration

IM

Side effects Pain & redness at site, fever

Alternative vaccine PPV23 (Pneumococcal Polysaccharide)


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Meningococcal Vaccine

Prevents bacterialmeningitis causedby Neisseria

meningitidis Groups A, C, Y, W-

135

Risk factors Intimate & household

contact Dormitory living Travelers Militar

Storage Refrigerate

Administration SQ

Side effects Pain & redness at site

Headache, malaise,fever

Protective Efficacy 85%


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Typhoid vaccine

Two typhoid vaccines are currently available for use

(Killed TAB vaccine is replaced by the newer vaccine)

1. an oral, live-attenuated vaccine (Vivotif Berna(tm) vaccine, manufactured fromthe Ty21a strain of S. typhi by the Swiss Serum and Vaccine Institute)

Oral Ty21a (Gal E mutant) Primary vaccination with oral Ty21a vaccine consists of a total of four capsules,one taken every other day. Repeat the series every five years if needed forcontinued coverage.

2. a capsular polysaccharide vaccine for injection (Typhim Vi(tm), manufactured byPasteur Merieux).

Typhim ViPrimary vaccination with Typhim Vi consists of one injection givenintramuscularly. Repeat this every two years if needed for continuedcoverage.

Protective efficcacy 50%-80% of recipients.


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Bacillus of Calmette and Gurin (BCG)vaccine

Reduce mortality and morbidity in Children< 5years old

Two meta-analyses of the published results of BCGvaccine clinical trials and case-control studies confirmedthat the protective efficacy of BCG for preventing seriousforms of TB in children is high ( >80%).

These analyses, however, did not clarify the protective

efficacy of BCG for preventing pulmonary TB inadolescents and adults; this protective efficacy isvariable and equivocal .

Cholera vaccine


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Cholera vaccine

Whole cell killed vaccineWhole cell killed vaccine + B subunit vaccine (WC/rBS)Live attenuated vaccine CVDHg103R

Two recently developed vaccines for cholera are licensed andavailable are- Dukoral, Biotec AB- Mutacol, Berna.

Both vaccines appear to provide a somewhat better immunity andfewer side-effects than the previously available vaccine.

Vaccine Protective Efficacy in the first six months

Vaccine Protective Efficacy 50-60% in three years ( Alsoeffective against ETEC)

Not effective against O139


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Lyme disease

Prevents Lyme disease caused by Borreliaburgdorferi transmitted by ticks

Used in persons over 15 years Vaccine not 100% effective; Tick bite protectionrecommended

Series of 3 vaccines should be completedbefore tick season (before April)

Storage Refrigerate

Administration - IM


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Vaccine against Anthrax

Vaccine for humans: ( avirulent and nonencapsulated) sublethal amounts of thetoxin produced

Licensed in the U.S. is a preparation of the protective antigen (PA)

Dose: A. 3 doses subcutaneously at the interval of 2 wksB. Followed by three additional doses at 6,12 and 18 monthsC. Annual booster dose

Professionals ( Veternarians, butcher, Zoo keeper, Wild life workers, Forestguards, Military personnels )

Vaccine against Plague

Available since 1896Efficacy not determined in proper studiesTwo vaccines :

Killed vaccine : 2 dose at 7-14 days interval, booster at 6 monthsLive vaccine : Y. pestis ( Ottens Tjiwidej, EV 76 strain) No longer used


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Other Infant Vaccines

Combination Vaccines

Hep-B and Hib (Comvax) Not used in infants under 6 weeks Not used if mother HBsAg+

DTaP and Hib (TriHIBit) Used for 4 th dose only


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Special Issues for InfantVaccination

Pre-term birth Pre-term infants should be

vaccinated at the samechronological age andaccording to schedule asfull-term infants andchildren.

Birthweight and size are notfactors to postponevaccination.

Divided or reduced dosesare not recommended.

Breastfeeding Breastfed infants are

vaccinated with thesame schedule. Breastfeeding is not

a contraindication forvaccination.


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Vaccine Development

During the 20 th century, several infectiousdiseases have been eliminated or reduceddramatically through the introduction ofvaccines.

Current bacterial vaccine development Tuberculosis Foodborne bacterial infections

Anthrax On-going work to improve current vaccines

Needle-free technology


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Adverse Events

Adverse Event Any event following a

vaccine

May be a true adversereaction, or onlycoincidental

May be local,systemic, or allergic

Adverse Reaction Unintended effect

caused by the vaccine May be

contraindication forfuture doses

Side Effect Common event to be

expected in percentageof recipients

Usually not serious Not contraindication for

future doses


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VACCINE DEVELOPOMENT

Vaccine licensure is a lengthy process that may last up to 10 years.

1. Laboratory studies : Safety and Immunogenicity Studies

Clinical trials

2. Phase I trial : Phase One trials are small, involving only 20-100 volunteers. Tocontinue to gather information on efficacy and safety of each vaccine,

3. Phase II trial : Phase Two trials are larger (with several hundredvolunteers), and last anywhere from a few months to a few years.

4. Phase III trial : Phase Three trials have several hundred to several thousandparticipants and typically last many years.

5. Phase IV trial: Vaccine is licensed and marketed. Data regarding side effectsare collected


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Edward Jenner
http://www.med.sc.edu:85/lecture/Image119.gif


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Live Attenuated Vaccines

Attenuated (weakened) form ofthe "wild" virus or bacteria

Must replicate to be effective

Immune response similar tonatural infection

Usually effective with one dose


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Advantages :

Very close to infectious agentImmune response similar to natural infection

Disadvantages :

Severe or fatal reactions possibleReversion to pathogenic (wild) formInterference from circulating antibodyStability

Current ly avai lab le l ive a t tenuated vaccines :

Viral: measles, mumps, rubella, yellow fever, vaccinia, varicellaBacterial: BCGRecombinant Typhoid vaccine


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Advantages :NonreplicatingNoninfectiousMinimal interference from circulating antibody

Disadvantages :Immune response mostly humoral

Antibody titer falls over timePrincipal antigen may not be well definedRequire multiple doses.

The first primes the immune system.The protective response after occurs after the second or third dose.Boosters are often necessary.

Current ly avai lab le inact ivated vaccines :

Viral: influenza, polio, rabies, hepatitis ABacterial: typhoid, cholera, plagueFractional vaccines: hepatitis B, influenza, acellular pertussisToxoids: diphtheria, tetanus, botulism, acellular pertussisPure polysaccharides: pneumococcal, meningococcalPolysaccharide conjugates: Haemophilus influenzae type b, pneumococcal


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Combination Vaccines

Whole cell DTP - Hib- Tetramune- ActHIB/DTP

DTaP - Hib (for 4th dose)- TriHIBit

Hepatitis B - Hib- COMVAX

Documents

Bacterial Vaccine