Vaccines1 Chapter 14 Also see on-line Influenza resource at nes.htm The Parents' Guide to Childhood Immunizations.

Vaccines 1

Vaccines

Chapter 14

Also see on-line Influenza resource at http://www.influenzareport.com/ir/vaccines.htm

The Parents' Guide to Childhood Immunizations http://www.cdc.gov/nip/publications/Parents-Guide/2005-parents-guide.pdf

Self-Test Questions:Intro: bothA: 1 – 5, 7, 8B: 1 - 8C - G: all

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Edward Jenner and the origin of vaccination

Small pox caused by ‘variola virus’

Induced immunity dates to ancient Chinese-- practiced ‘Variolation’-- brought to England in 1700s-- lead to the ‘Royal experiment’

Jenner discovered protective effect of cow pox-- ‘vaccinia virus’ -- ‘vacca’ Latin for cow - vaccination

WHO irradicated small pox in 1970s

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What are different types ofimmunization?

Passive Immunization-- direct transfer of protective antibodies-- no immunological memory

Active Immunization-- activation of immune response-- immunological memory

Therapeutic Immunization-- treat existing disease

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Passive Immunization to treat Fetal Erythroblastosis Conditions: mother Rh—; father, 1st and 2nd fetuses are Rh+RhImmune hemolysisRhogam

Given 24-48 hours after 1st pregnancy

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Active Vaccination: What are some important considerations in the design of vaccines?

Characteristics of pathogen & disease Intra- vs extra-cellularshort or long incubationacute or chronic diseaseAntigenic stabilityroute of infection

Characteristics of vaccineefficacyappropriate responseboostersafetystability, cost

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What are the recommended childhood vaccines?

Combined vaccines

Why are boosters needed?

Other vaccines for special needs

TB, anthrax, plague, yellow fever, etc

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Is 100% efficacy necessary? -- “herd immunity”

Cases per Year Decrease before in in Cases(average) 2003 per Year

Diphtheria 175,885 1 99.9% Hib (<5 yrs old) 20,000 (est.) 259 98.8% Measles 503,282 56 99.9% Mumps 152,209 231 99.9% Pertussis 147,271 11,647 92.1% Polio (paralytic) 16,316 0 100.0% Rubella 47,745 7 99.9% Smallpox 48,164 0 100.0% Tetanus 1,314 20 98.5%

Sources CDC. Impact of vaccines universally recommended for children — United States, 1900-1998. MMWR 8(12):243-8 CDC. Notice to Readers: Final 2003 Reports of Notifiable Diseases. MMWR

2004;53(30):687

How effective are vaccines?

Vaccine “efficacy” incidence among those administered

1- ------------------------------------------- -------------------------------------------

incidence among those not administered -- e.g., 60% efficacy-- depends upon population, age, etc

Example efficacies Diphtheria: 87%-96% Tetanus: >90% Oral polio: 90%-100% Mumps/Measles/Rubella: 90%-95%

HIV vaccine trials 150 vaccines developed 6 have made it to efficacy testing 2009: 1st with efficacy (31%) [2007 had negative efficacy]

Malaria vaccine trial 2011: 45 – 56%

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How are vaccines made?

Dead (inactivated) pathogensIPV – Inactivated polio vaccine – ‘Salk’ vaccine[old pertussis of DPT -- Bordetella pertussis]

Live attenuated pathogensMMR – measles, mumps, rubella virusesOVP -- oral polio vaccine – ‘Sabin’ vaccine

Subunit / Peptide components HBsAG -- Hepititis B surface antigenFlu – purified HA & NA antigens

Conjugates (polysaccharides coupled to protein carrier)HiB – Haemophilus influenzae type BPCV – pneumococcal conjugate vaccine

ToxoidsDTaP -- diphtheria, tetanus toxoids

[ + “acellular pertussis” molecular component]

Remember Adjuvants? -- increase immune response e.g., aluminum hydroxide

Cell cultured virus

McGraw-HillVaccines

Vaccines 9

What are pros and cons of different types of vaccines?

Dead (inactivated) pathogensprosmay be safer; more stable than attenuated

consweaker cell mediated response; boosterscontaminants – pertussis endotoxin in old DPT

Live attenuated pathogensprosbetter cell-mediated response

consreversion -- Sabin polio (Types 1 & 2)infection in immunodeficient patientsless stable

Molecular components prosNo living pathogen presentvery stable

consfewer epitopesweaker cell mediated response

Vaccine type Example reactions

Vaccines from Chicken eggs and cell cultures

Allergic reactions

Contaminating pathogens

Vaccines with Preservatives

Allergic reactions

Live attenuated Susceptibility during preganncy and among immunodepressed

Dead whole cell Contamination with toxins

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Why do we not have vaccines for serious protozoal diseases

-- malaria, African sleeping sickness

Plasmodium causes Malaria-- Anopholes mosquito is vector

Trypanosoma cause ASS-- tsetse fly is vector

Complex life cycles

Chronic diseases

Undergo “Antigenic Shift”

Trypanosoma carries ~1000 VSG genes(variant surface glycoprotein)

~1% of parasites shift AG

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Influenza: the disease

Principal virus subtypes -- A & B Key surface antigens

Hemaglutinin -- HANeuraminidase – NA

-- numbered 1,2,3, etc

Causes of seasonality unclear:Δ antigenicity/ infectiousnesssocial interactionsenvironmental conditions

Current circulating formsH3N2*, H1N1, H1N2, ~36K deaths~200,000 hospitalizations

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Influenza con’t:

Circulating stains vary annually-- “antigenic drift”-- vaccine must accommodate

Recent vaccines containA -- New Caledonia/20/99 (H1N1) A -- Wisconsin/67/2005 (H3N2) B -- Malaysia/2506/2004

Vaccines typesInjection – inactivated whole virus or

purified HA & NA antigensNasal spray “FluMist”

-- cold adapted attenuatedPrepared in eggs

Capacity only ~ 300 x 106 doses

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Pandemic Flu

“Antigenic-Shift” can occur

History1918 Spanish Flu (H1N1; 40 mil dead)1957 Asian Flu (H2N2; ~1 mil+ dead1968 Hong Kong Flu (~0.75 mil dead)

-- AG-shift from H2N2 to H3N2

Swine Flu 2009 H1N1 vaccine (influenza A/California/07/2009)

15 μg HA or106.5-107.5 pfu of live attenuated virus

Challenges to vaccinationDevelopment timeProduction capacity (use of eggs?)DistributionEconomicsVaccination strategy

Current spread of H5H1

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New Vaccination Strategies

DNA vaccines DNA for an AG injected

-- expressed in cells

ProsBoth arms respondDNA is very stableNo pathogen involved

ConsStill experimentalLimited epitopes

Recombinant vectors

e.g., HIV genes in an Adenovirus vector