Immunizations June 5, 2015

Brenda Ormesher, MD Infectious Disease

Peacehealth Medical Group Springfield, OR

Disclosures

None

Goals

Understand basic public health impact of immunization

Recognize types of vaccinations available

Identify resources available for identifying CDC recommended immunizations

Discuss differences and rationale for use of specific vaccination formulations in practice

Introduction

Vaccine

vac·cine/vakˈsēn/

(Noun) a substance used to stimulate the production of antibodies and provide

immunity against one or several diseases, prepared from the causative agent

of a disease, its products, or a synthetic substitute, treated to act as an antigen

without inducing the disease.

History

One of the great public health achievements in human history

Inoculation against smallpox was practiced 2000 years ago but modern concept credited to Edward Jenner (1796)

Now 23 FDA approved vaccine-preventable diseases

http://www.immunize.org/catg.d/p4037.pdf

General Characteristics of Vaccines

Components of Vaccine Antigens

component derived from disease- causing organism which trigger protective immune response

Stabilizers

Maintain effectiveness during storage

Factors affecting stability include temperature and pH

Include magnesium chloride (OPV), magnesium sulfate (RSV, measles), lactose-sorbitol and sorbitol- gelatin

Adjuvants

Added to vaccines to stimulate production of antibodies

Several hundred different types

Antibiotics

Trace amounts used in manufacturing to prevent bacterial contamination of tissue growth cells for viruses

Trace amounts (25 micrograms neomycin in MMR and IPV)

Preservatives

Multidose vaccines to prevent bacterial and fungal growth

Include thiomersal, formaldehyde (purification process removes almost all formaldehyde, <0.02% per dose)

Routes of Administration

http://vaccine-safety-training.org/adverse-events-causes.html

Types of Vaccines

Live, attenuated

Inactivated/ killed

Toxoid (inactivated toxin)

Subunit/ conjugate

DNA vaccine

Recombinant vector

Live, attenuated

• Living microbe that has been weakened in the lab

• Should not be given in immunocompromised host

• Closest to natural infection

• Elicit strong cell-mediated and antibody response

• Life long immunity with only 1 or 2 doses (similar immunogenicity as wild-type pathogen)

Examples: MMR (measles, mumps, rubella)

Varicella (chickenpox)

Influenza nasal spray

Rotavirus

Zoster (shingles)

Yellow fever

Tuberculosis (BCG)

Oral polio vaccine (OPV)

Live, attenuated Vaccines

http://vaccine-safety-training.org/live-attenuated-vaccines.html

Inactivated, killed

Produce inactivated vaccine by killing the microbe with chemicals, heat, or radiation

More stable and safe than live vaccines (dead microbes cannot mutate)

Stimulate a weaker immune system response than live vaccines

Requires booster shots to maintain immunity

Examples:

Polio (IPV)

Hepatitis A

Whole-cell pertussis (wP)

Rabies

Inactivated, killed Vaccines

http://vaccine-safety-training.org/inactivated-whole-cell-vaccines.html

Toxoid (inactivated toxin)

For bacteria that secrete toxins (toxin must be main cause of illness)

Inactivate toxins by treating with formalin

To increase immune response the toxoid is absorbed to aluminum or calcium salts (serve as adjuvant)

Produces antibodies that lock onto & block the toxin

Examples:

Diphtheria, tetanus (part of DTaP)

Toxoid Vaccines

http://vaccine-safety-training.org/toxoid-vaccines.html

Subunit Protein-based, Polysaccharide, Conjugate

Use only part of a target pathogen (no live components)

Protein or polysaccharide- Uses part of target pathogen to provoke a response from the immune system Conjugate- Link antigens or toxins that immune system will recognize to the polysaccharide coating of bacteria

No guarantee that immunological memory will be formed in correct manner

Examples: Influenza (injection)

Haemophilus influenza type b (Hib)

Pertussis (part of DTaP)

Pneumococcal

Meningococcal

Human papillomavirus (HPV)

Subunit:

Polysaccharide versus Conjugate

Polysaccharide

Little or short-lived impact on carriage of bacteria

Decreasing immune response with time (needs boosters)

Limited ability to protect children under 2 years

Conjugate

Enhances the immune response and long term recognition

Protective immune response in infants

Minimizes hyporesponsiveness

Harder to design/ develop

Polysaccharide vs Conjugate Vaccines

http://www.nature.com/nri/journal/v9/n3/fig_tab/nri2494_F1.html

Subunit (purified antigen) Vaccines

http://vaccine-safety-training.org/subunit-vaccines.html

CDC Immunization Recommendations

Recommended adult immunization schedule, by vaccine and age group

CDC 2015 Adult Immunization Schedule

Vaccines that might be indicated for adults based on medical or other indications

CDC 2015 Adult Immunization Schedule

“There’s an app for that”

• Free!

• Available from App store for

iOS 5.0 or later or Google Play

for Android 2.1

• http://www.cdc.gov/vaccines/s

chedules/hcp/schedule-

app.html#download

Vaccine Specific Information

Vaccine-Preventable Diseases

Adenovirus type 4 & 7

Anthrax

Chickenpox (Varicella)

Diphtheria

Hepatitis A

Hepatitis B

Hib (Haemophilis influenza type b)

HPV (Human Papillomavirus)

Influenza

Japanese encephalitis

Measles

Meningococcal

Mumps

Pertussis (Whooping cough)

Pneumococcal

Poliovirus

Rabies

Rotavirus

Shingles (Herpes zoster, varicella)

Tetanus

Tuberculosis

Typhoid fever

Yellow fever

Influenza

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/us-vaccines.pdf

Which influenza vaccine is right for my patient?

That depends….

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm#Tab

Does your patient have an egg allergy? Cost $32/ dose

Is your patient a pediatric patient?

In pediatrics demonstrated superior efficacy in live attenuated vaccine

reduction of 55% in culture confirmed influenza cases in ages 6 to 59 months

52% increased protection in children age 6 to 71 months)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

Is your patient age 6 months to 2 years?

Give Fluzone

In a previously unvaccinated child (< 8 years old) give 2 doses of influenza vaccine at least 4 weeks apart

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

Is your patient age 2 to 49 years old and have special medical conditions?

Pregnant?

Immunosuppressed?

Egg allergy?

Children age 2 to 17 years receiving aspirin?

Children age 2 to 4 years who have asthma with wheezing in past 12 months?

Influenza antiviral medications in past 48 hours?

Care for severely immunosuppressed person who require a protective environment?

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

Is your patient age 2 to 49 years old and have special medical conditions?

Yes: do not give live attenuated vaccine (FluMist), give inactivated influenza vaccine

No: give FluMist (cost $22 per dose)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm

Is your patient over 65 years old?

Inactivated influenza vaccine high dose (60 mg of hemagglutinin per strain) induced a significantly higher antibody response and provider better protection against lab-confirmed illness than standard inactivated influenza vaccine (15 mg of hemagglutinin per strain)

Cost of high dose influenza vaccine $30 vs $10 for standard dose

DiazGranados, C. Et al. “Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults.” NEJM 2014; 371:635-645.

Vaccine Effectiveness

Vaccine effectiveness decline post-vaccination

By age: Vaccine effectiveness in < 65 years estimated at 44%, vaccine effectiveness > 65 years estimated at 19%

By time: Vaccine effectiveness in first 100 days 61%, between 100 and 119 days was 42%, after 120 days was 0%

Castilla J, et al. “Decline in Vaccine Effectiveness with Time After Vaccination, Navarre, Spain, Season 2011/12.” Eurosurveillance, Volume 18, Issue 5, 31Jan2013.

Quadrivalent versus Trivalent

Rationale for quadrivalent: historically influenza vaccines contain only one strain of B virus although though there are two different lineages of B strains that circulate most seasons

Benefit: improved coverage of B strain which could account for 1-44% of influenza cases (based on data from preceding 10 years)

Negative: Cost ($15 for quad vs $10 for tri), supply

Pneumococcal

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/us-vaccines.pdf

₊ Pneumovax (PPSV23)- Pneumococcal polyvalent (polysaccharide) vaccine covering 23 serotypes, cost $85/ dose

₊ Prevnar (PCV13)- Pneumococcal conjugate vaccine covering 13 serotypes, cost $150/ dose

Pneumococcal Recommendations

Recommendation for adults 65 years or older: see diagram

Recommendations for adults 19 years or older with no history of PCV13: • CSF leak, cochlear implant, sickle cell

disease, function or anatomic asplenia, congenital or acquired immunodeficiency, HIV infection, chronic renal failure, nephrotic syndrome, leukemia, Hodgkin disease, generalized malignancy, long-term immunosuppressive therapy, solid organ transplant, multiple myeloma

Bonten M, Bolkenbaas M, Huijts S, et al. Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Abstract no. 0541.

Pneumonia 2014;3:95. https://pneumonia.org.au/public/journals/22/PublicFolder/ABSTRACTBOOKMASTERforwebupdated20-3-14.pdf .

Meningococcal

http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/us-vaccines.pdf

Meningococcal Disease- Worldwide

http://www.meningitisinfo.com/Epidemiology_ssi.aspx

Meningococcal A, C, W-135 and Y

Menomune

Polysaccharide vaccine

Licensed for data on A & C strains (not enough date for W-135, Y)

Recommended for adults who require single dose only (travelers, military recruits)

Cost $125/ dose

Menactra

Polysaccharide conjugate vaccine

Licensed for A, C, Y, W-135

Asplenia, complement deficiencies, microbiologist, frequent international travelers to high endemic regions (African meningitis belt, Hajj)

Cost $100/ dose

Menveo

polysaccharide conjugate vaccine

Licensed for A, C, Y, W-135

Asplenia, complement deficiencies, microbiologist, frequent international travelers to high endemic regions (African meningitis belt, Hajj)

Cost $120/ dose

Meningococcal B

Trumenba Composed of two recombinant lipidated factor H binding protein

(fHBP) variants from N. meningitidis serogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively)

Series of 3 shots at 0, 2 and 6 months

Cost $120/ dose

Bexsero Composed of 4 distinct antigens including factor H binding protein

(fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA), and PorA P1.4 immunodominant antigen of OMV NZ (strain NZ98/254)

Series of 2 shots at least 1 month apart

Cost $160/does

Human Papillomavirus

Cervarix

Viral protein subunit vaccine

Covers serotype 16 and 18 (may provide cross protection for 31, 33, 45,52)

Contains novel adjuvant so may be responsible for great antibody response (unknown)

Series of 3 shots at 0, 1-2 and 6 months

Cost $130/ dose

Gardasil

Viral protein subunit vaccine

Covers serotype 6, 11, 16 and 18 (may provide cross protection for 31, 45)

Series of 3 shots at 0, 2 and 6 months

Cost $150/ dose

Gardasil 9

Viral protein subunit vaccine

Covers serotype 6, 11, 16, 18, 31, 33, 45, 52 and 58

Series of 3 shots at 0, 2 and 6 months

Cost $160/ dose

http://www.ganfyd.org/index.php?title=File:HPVCervicalCancer.png

Questions/ Comments? Email: BOrmesher@peacehealth.org Thank you!