1. Kenneth McCall, BSPharm, PharmD, BCGP Associate Professor | UNE
Immunization Update 2017
Kenneth McCall, BSPharm, PharmD, BCGP
Associate Professor | UNE

2. Objectives
Discuss the gap between current rates and Healthy People 2020 goals for vaccinations.
Categorize each of the CDC recommended flu vaccines based upon live/inactivated, route, prep., and storage.
Discuss the influenza vaccines for
Recognize the ACIP recommendations for pneumococcal vaccines.
Compare the GSK zoster vaccine with Merck’s Zostavax.
Apply ACIP recommendations and FDA approved indications for the CDC recommended vaccines.
Recognize federal and state laws that regulate vaccine administration.

3. CDC ACIP 2017 Recommended Adult Immunization Schedule

5. Altered Immunocompetence: Inactivated Vaccines-Safety
All inactivated vaccines can be administered safely to persons with altered immunocompetence.

6. Altered Immunocompetence: Live Vaccines-Safety
Severe complications have followed vaccination with certain live, attenuated viral and live, attenuated bacterial vaccines among persons with altered immunocompetence. Persons with most forms of altered immunocompetence should not receive live vaccines (MMR, varicella, MMRV, LAIV, zoster).
Immunosuppressive steroid dose is considered to be daily receipt of 20 mg or more prednisone or equivalent for two or more weeks. Vaccination should be deferred for at least 1 month after discontinuation of immunosuppressive steroid therapy.

7. Should Immunocompromised Patients or Those Who Will Undergo Immunosuppression Receive Herpes Zoster Vaccine?
Zoster vaccine should be given to patients aged ≥60 years if it can be administered ≥4 weeks before beginning highly immunosuppressive therapy.
Zoster vaccine should not be administered to highly immunocompromised patients.
Zoster vaccine should be administered to patients aged ≥60 years who are receiving therapy considered to induce a low level of immunosuppression 
IDSA Guidelines. Clin Infect Dis. 2014;58(3):e

8. Patients with high-level immuno-suppression include those:
Primary immunodeficiency disorder (eg, severe combined immunodeficiency),
receiving cancer chemotherapy,
within 2 months after solid organ transplantation,
with HIV infection with a CD4 T-lymphocyte count <200 cells/mm3 for adults and adolescents and percentage <15 for infants and children,
receiving daily corticosteroid therapy with a dose ≥20 mg (or >2 mg/kg/day for patients who weigh <10 kg) of prednisone or equivalent for ≥14 days, and
receiving certain biologic immune modulators, that is, a tumor necrosis factor-alpha (TNF-α) blocker or rituximab
those receiving methotrexate (MTX) >0.4 mg/kg/week, azathioprine >3 mg/kg/day, or 6-mercaptopurine >1.5 mg/kg/day 
Clin Infect Dis. 2014;58(3):e

9. Select the FALSE statement regarding vaccine use in immunocompromised patients.
Inactivated vaccines are more likely to be unsafe
Live vaccines are more likely to be unsafe
Inactivated vaccines may be less effective in this population
Live vaccines may be less effective in this population

10. Which medication would categorize a patient as high-level immunosuppression?
Prednisone 20 mg QD x 10 days
Low dose TNF-α blocker
0.2 mg/kg/wk MTX
Azathioprine 1.5 mg/kg/day

11. Maine Pharmacist-Administered Immunization Regulations
No Rx Required
Rx Requireda
Rx or Protocol
Not permitted
Adult (≥18 years) with PCPb
Influenza
✓-RPh or Intern
Other Vaccinesc
Adult (≥18 years) without PCP
Child < 18 years ✗
Child 7-17 years
✓-RPh only
Child <7 years
Sources: Maine H.P L.D and H.P. 836 L.D. 1218
Intern administration permitted as indicated under direct supervision of licensed pharmacist
a Verbal/phone authorization acceptable
b Primary care physician or existing relationship with a nurse practitioner or an authorized practitioner in Maine
c All vaccines licensed by the US FDA recommended by the CDC ACIP

12. Influenza Vaccines

13. Influenza A and B are the two types of influenza viruses that cause epidemic human disease. Since 1977, influenza A (H1N1 and H3N2) viruses and influenza B viruses have circulated globally.1
The influenza A virus is composed of a viral genome covered by a protein shell, the capsid. A lipid bi-layer envelops the capsid, as shown in the figure.2
Influenza A viruses are categorized into subtypes on the basis of two surface antigens: hemagglutinin and neuraminidase.1
Within the envelope is the influenza genome, which is organized into 8 pieces of single-stranded RNA.2
1. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2010;59(RR-8):1–62.
2. Molecular Expressions: Cell Biology and Microscopy Structure and Function of Cells and Viruses. Accessed April 15, 2012. 13

15. ACIP Recommendations 2017-18 Influenza Season
For 2017–18, U.S.-licensed trivalent influenza vaccines contain:
A/Michigan/45/2015 (H1N1)pdm09-like virus
A/Hong Kong/4801/2014 (H3N2)- like virus
B/Brisbane/60/2008-like (B/Victoria lineage) virus.
This represents changes in the influenza A (H1N1) virus as compared with the 2016–17 season. Quadrivalent influenza vaccines will contain these vaccine viruses, and a B/Phuket/3073/2013-like (B/Yamagata lineage) virus.
All persons aged ≥6 months should receive influenza vaccine annually.
Afluria may be used in persons ≥5 years old.
Pregnant women may receive any licensed, recommended, age-appropriate vaccine.
Live attenuated influenza vaccine (LAIV4) should still not be used.
The current influenza vaccine has been 48% (95% confidence interval [CI], 37% - 57%) effective in preventing influenza-related medical visits in all age groups, the CDC reported on February 17. According to the report, the vaccine was 43% (95% CI, 29% - 54%) effective against influenza A (H3N2) viruses and 73% (95% CI, 54% - 84%) effective against influenza B–related illness.

16. Age Indication for Influenza Vaccines: United States, 2017-2018
0.5-2 years 2
years 3
4-8
9-17
18-49 years
50-64 years
65+
Fluzone / Fluzone Quad ✓
Flumist Quad
Fluarix Quad
FluLaval Quad
Fluvirin
Afluria1 +-
Flucelvax Quad
Flublok2
Fluzone Intradermal Quad
Fluzone High-Dose
Fluad Adjuvated Trivalent
Afluria is now approved for 5 years and up
“A licensed, age-appropriate vaccine should be used.”
Age indication via needle/syringe is >5 years and by Pharmjet needle-free injection is years.
FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+).

17. New Influenza Vaccines:
Fluad ® (Seqirus) Adjuvanted trivalent inactivated vaccine
FDA approved November, 2015
People ages 65 and older
Flucelvax® (Novartis)– quadrivalent inactivated vaccine grown in mammalian cells.
FDA approved May, 2016|
Adults 4 years and older
Flublok® (Protein Sciences Corp.) – inactivated, trivalent, recombinant vaccine.
FDA approved March 2013
People ages 18 years and older
Doesn’t list “severe allergic reaction to egg protein” in the contraindications

18. Which of the following is the predominant flu strain of 2017-18?
Type B strain in trivalent vaccine
Type B strain not in trivalent vaccine
Type A H1N1 strain
Type A H3N2 strain

19. Adjuvanted Trivalent Inactivated Influenza Vaccine Fluad®

20. New Influenza Vaccines:
Fluad ® (Seqirus) –
Adjuvanted, inactivated, trivalent vaccine
FLUAD also contains MF59C.1 adjuvant (MF59®), a squalene based oil-in-water emulsion.
FDA approved November 2015
People ages 65 years and older

21. % of adults >65 years with local adverse reactions in days 1-7

22. % of adults >65 years with systemic adverse reactions in days 1-7

23. Seroconversion Rates at Day 22

24. Difference in seroconversion rate (95% CI) at day 22

25. Inactivated Influenza Vaccine (IIV) Quadrivalent Fluarix®, Fluzone®, FluLaval®, Fluzone Intradermal®

26. Influenza Positive Specimens Reported by USPH Labs, Cumulative, 2016-2017 Season
The flu vaccine's effectiveness may vary depending on age, health, and immune status and how well scientists identity circulating viruses.
In , vaccine effectiveness was under 20%.

27. Administration Fluarix Quadrivalent®: 0.5-mL dose IM - deltoid
1 inch, 25 gauge needle

28. Quadrivalent Influenza Vaccines contain which of the following?
Four type A strains
Two type A strains, 1 type B, & 1 type C
Two type A strains & 2 type B strains
Four type B strains

29. Inactivated, Trivalent Recombinant Vaccine Flublok®

30. New Influenza Vaccines:
Flublok® (Protein Sciences Corporation)– trivalent inactivated vaccine grown in insect cells rather than chicken embryo cells.
FDA approved November, 2013
Adults 18 years and older (new indication as of April 2015; previously years).
Doesn’t list “severe allergic reaction to egg protein” in the contraindications*
*Flublok contains no egg proteins, antibiotics, or preservatives. The stoppers used for the single-dose vials are not made with natural rubber latex.

31. Vaccine Efficacy against Culture-Confirmed Influenza in Healthy Adults 18-49 years

32. Frequency of Local and Systemic Reactions within 7 days of Flublok or Placebo in Adults 18-49 years

33. ACIP Recommendations for flu vaccination of person who report egg allergy.

34. Administration Flublok®: 0.5-mL dose IM - deltoid
1 inch, 25 gauge needle

35. Select an influenza vaccine for a healthy 37-year-old woman with severe egg allergy.
Flublok
Flumist
Fluzone
Fluarix

36. Influenza Vaccines: Summary

37. Age Indication for Influenza Vaccines: United States, 2017-2018
0.5-2 years 2
years 3
4-8
9-17
18-49 years
50-64 years
65+
Fluzone / Fluzone Quad ✓
Flumist Quad
Fluarix Quad
FluLaval Quad
Fluvirin
Afluria1 +-
Flucelvax Quad
Flublok2
Fluzone Intradermal Quad
Fluzone High-Dose
Fluad Adjuvated Trivalent
“A licensed, age-appropriate vaccine should be used.”
Age indication via needle/syringe is >5 years and by Pharmjet needle-free injection is years.
FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+).

38. Characteristics of Influenza Vaccines: United States, 2017-18
Live
Mercury
Egg Protein
Latex
Fluzone / Fluzone Quad ✓1 ✓
Flumist Quad
Fluarix Quad
FluLaval Quad
Fluvirin ✓3
Afluria
Flucelvax Quad ✓2
Flublok
Fluzone Intradermal Quad
Fluzone High-Dose
Multi-dose vials contain mercury. Single-dose prefilled syringes are mercury-free.
Estimated to contain <50 femtograms (5x10-8 mcg) of total egg protein per 0.5 ml dose.
Syringe tip may contain natural rubber latex.

39. Route of Admin. for Influenza Vaccines: United States, 2017-18
Young Children*
Older Children
Adults
Fluzone / Fluzone Quad
IM Thigh
IM Deltoid
Flumist Quad
Intranasal
Fluarix Quad
FluLaval Quad
Fluvirin
Afluria
Flucelvax Quad
Flublok
Fluzone Intradermal Quad
ID Deltoid
Fluzone High-Dose
*Generally, less than 7 years old.

40. CONSIDERATIONS Vaccine Patient Group
Quadrivalent (Fluzone Quad, Fluarix, Flulaval)
Everyone age appropriate ≤64 years old
Trivalent (Fluad, Fluvirin)
Age appropriate 6 months to 64 year olds and no supply or insurance coverage of quadrivalent
Flublok
Severe egg allergy
Fluzone HD, Fluad Adjuvated
≥ 65 years old
Fluzone Intradermal, Afluria
Age appropriate and fear of needles
Flumist
Not recommended
*Any age-appropriate flu shot is the best flu shot

41. Who should get the flu shot?
You
All of the above

42. Universal Flu Vaccine on the Horizon
Will be the first in the world to fight all types of the virus
Uses proteins found on the core of the virus, rather than the surface
These proteins do not change as often; vaccine may provide protection for years
Stimulates the immune system to boost T-cells, rather than antibodies

43. Universal Flu Vaccine on the Horizon
Developed by Oxford University’s Jenner Institute and Vaccitech
Two-year clinical trial is just beginning
500 patients in UK this season
1500 more next year

44. Pneumococcal Vaccine PPSV23 / Pneumovax® PCV13 / Pnevnar®

45. Pneumococcal Disease Complex immunization recommendation for adults
Pneumococcal disease is caused the bacterium Streptococcus pneumoniae
Clinical Features
Pneumonia
Otitis media
Sinus infections
Bacteremia
Meningitis
Risk Factors
Asplenia
Chronic heart, pulmonary, liver, or renal disease
Cigarette smoking
Cerebrospinal fluid leak
Age less than 2 years, or 65 years and older
Complex immunization recommendation for adults
There are different types of pneumococcal disease, such as lung infections (pneumococcal pneumonia), blood infections (bacteremia), infections of the covering of the brain and spinal cord (pneumococcal meningitis), and middle ear infections (otitis media). Pneumococcal disease is a leading cause of vaccine-preventable illness and death in the United States.
Pneumonia is the most common presentation of pneumococcal disease among adults – incubation of pneumonia is 1-3 days – it is characterized by abrupt onset of fever, rigors, chills, pleuritic chest pain, productive cough, dyspnea, tachypnea, hypoxia and diagnosed by x-ray imaging and symptoms
However, calling the pneumococcal vaccine the “pneumonia vaccine” can be misleading – one of the greatest benefits of receiving the pneumococcal vaccine is the protection against invasive pneumococcal disease, or “IPD” such as bacteremia or meningitis. The term “invasive” refers to infection of an area of the body that is normally bacteria free – such as the blood stream or the cerebrospinal fluid

46. Pneumococcal Vaccines
Pneumovax 23® (PPSV23, pneumococcal polysaccharide vaccine)
Prevnar 13® (PCV13, pneumococcal conjugate vaccine)
Pneumococcal polysaccharide vaccine is composed of purified preparations of pneumococcal capsular polysaccharide. The first polysaccharide pneumococcal vaccine was licensed in the United States in It contained purified capsular polysaccharide antigen from 14 different types of pneumococcal bacteria. In 1983, a 23-valent polysaccharide vaccine (PPSV23) was licensed and replaced the 14-valent vaccine, which is no longer produced. PPSV23 contains polysaccharide antigen from 23 types of pneumococcal bacteria that cause 88% of bacteremic pneumococcal disease. In addition, cross-reactivity occurs for several capsular types that account for an additional 8% of bacteremic disease.
The polysaccharide vaccine currently available in the United States (Pneumovax 23, Merck) contains 25 mcg of each antigen per dose and contains 0.25% phenol as a preservative. The vaccine is available in a single-dose vial or syringe, and in a 5-dose vial. Pneumococcal vaccine is given by injection and may be administered either intramuscularly or subcutaneously.
The first pneumococcal conjugate vaccine (PCV7) was licensed in the United States in It includes purified capsular polysaccharide of seven serotypes of S. pneumoniae (4, 9V, 14, 19F, 23F, 18C, and 6B) conjugated to a nontoxic variant of diphtheria toxin known as CRM197. In 2010 a 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in the United States. It contains the 7 serotypes of S pneumonia as PCV7 plus serotypes 1, 3, 5, 6A, 7F and 19A which are also conjugated to CRM197. A 0.5-mL PCV13 dose contains approximately 2.2 µg of polysaccharide from each of 12 serotypes and approximately 4.4 μg of polysaccharide from serotype 6B; the total concentration of CRM197 is approximately 34 µg. The vaccine contains 0.02% polysorbate 80 (P80), mg of aluminum as aluminum phosphate (AlPO4) adjuvant, 5mL of succinate buffer, and no thimerosal preservative. Except for the addition of six serotypes, P80, and succinate buffer, the formulation of PCV13 is the same as that of PCV7.
ABCs data indicate that in 2008, a total of 61% of invasive pneumococcal disease cases among children younger than 5 years were attributable to the serotypes included in PCV13, with serotype 19A accounting for 43% of cases; PCV7 serotypes caused less than 2% of cases.

47. ACIP Recommendations on Pneumococcal Vaccinations in Adults

48. Pneumococcal Vaccine Recommendations for Adults with Immunocompromising Conditions

49. Pneumococcal vaccine-naïve persons aged > 65 years
*minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks;
PPSV23 can be given later than 6-12 months after PCV13 if this window is missed.

50. Persons who previously received PPSV23 at age > 65 years
*minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks;
PPSV23 can be given later than 6-12 months after PCV13 if this window is missed.

51. Persons who previously received PPSV23 before age 65 years who are now aged > 65 years

52. A 65-year-old man who is pneumonia vaccine naïve
A 65-year-old man who is pneumonia vaccine naïve. What pneumonia vaccine(s) is/are recommended?
Pneumovax only
Prevnar only
Both; Pneumovax prior to Prevnar
Both; Prevnar prior to Pneumovax

53. A 56 yo woman takes TNF alpha blocker therapy for RA
A 56 yo woman takes TNF alpha blocker therapy for RA. Which of the vaccines is NOT recommended?
Inactivated influenza annually
Prevnar
Pneumovax at least 8 weeks after Prevnar
Zostavax
zostavax

54. Questions and Discussion

55. Add zoster slides

56. Preventing Shingles: Zostavax or Shingrix?
Kenneth McCall, BSPharm, PharmD
Associate Professor | UNE
Maine Pharmacy Association
Think of creative title

57. Clinical Presentation of Herpes Zoster1–3
Herpes Zoster Rash Follows a Dermatomal Distribution
© Phototake.
© Phototake.
© Dr. P. Marazzi / Photo Researchers, Inc.
Prodrome
Acute HZ Rash
Evolution of Rash
Complications?
Abnormal Skin Sensations
Headache
Photophobia
Malaise
Unilateral Dermatomal Rash
Maculopapules/Vesicles
Altered Sensitivity to Touch
Unbearable Itching
Cessation of New Vesicles
Pustulation
Scabbing
Cutaneous Healing
Neurologic
Cutaneous
Ophthalmic
Visceral (rare)
Clinical Presentation of Herpes Zoster
The presentation and subsequent resolution of zoster may not always be straightforward.
The zoster rash is often preceded by several days of a prodromal phase that is characterized by pain that may range from tingling and burning to severe sharp, stabbing, or lancinating. Headache, photophobia, and malaise may also occur.1,2
The zoster rash, itself, is generally limited to 1 unilateral dermatome. Frequently reported symptoms include altered sensitivity to touch, pain provoked by slight stimuli, and unbearable itching.1,2
Lesions usually last 7 to 10 days and the rash fully heals within 2 to 4 weeks.1
Complications of zoster may include postherpetic neuralgia (PHN), scarring, bacterial superinfection, cranial and motor neuron palsies, visual impairment, and hearing loss.1,3
Although most complications will resolve over time, some patients are refractory to treatments and may suffer permanent impairment.1,2,4
1. Weaver BA. J Am Osteopath Assoc. 2009;109(6 suppl 2):S2–S6.
2. Harpaz R et al. MMWR. 2008;57(RR–5):1–30.
3. Oxman MN. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge University Press; 2000:246–275.
4.Watson CPN et al. Pain. 1991;46:195–199.
Pain (varying severity)
“Aching”, “burning”, “stabbing”, “shock-like”
Oxman MN. In: Arvin AM et al, eds. Varicella-Zoster Virus: Virology and Clinical Management. Cambridge, UK: Cambridge University Press; 2000:246–275.
Weaver BA. J Am Osteopath Assoc. 2007;107(suppl 1):S2–S7. 3. Harpaz R et al. MMWR Morb Mortal Wkly Rep. 2008;57(RR-5):1–30.

59. Herpes Zoster is the reactivation of which virus?
Measles
Mumps
Rubella
Varicella 4

60. What is the most common longterm complication of herpes zoster?
Bell’s palsy
Postherpetic neuralgia
Vision loss
Myocarditis 2

61. Prevention of Zoster and Postherpetic Neuralgia
ZOSTAVAX®
(Zoster Vaccine Live)

62. Zoster Vaccine Indication
ACIP recommends routine vaccination of all persons aged >60 years with 1 dose of zoster vaccine.
NEW FDA LABELING: “ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of herpes zoster (shingles) in individuals 50 years of age and older.”
Persons who report a previous episode of zoster and persons with chronic medical conditions can be vaccinated unless those conditions are contraindications or precautions.
Zoster vaccination is not indicated to treat acute zoster.
Zostavax® [package insert]. Whitehouse Station, NJ: Merck; April 2011.
Recommendations of the Advisory Committee on Immunization Practices (ACIP)

63. Vaccine Contraindications
Allergy to neomycin or any vaccine component
Pregnancy
Immunocompromised status
AIDS or other clinical manifestations of HIV, including persons with CD4+ T-lymphocyte values <200 per mm3
malignant neoplasms affecting the bone marrow
chemotherapy or radiation within the last 3 months
Persons on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting two or more weeks

64. Storage and Handling Zoster vaccine must be stored frozen
The vaccine must be discarded if not used within 30 minutes after reconstitution.
New labeling: Zostavax may be stored and/or transported at fridge temp for up to 72 hours prior to reconstitution. Any unused vaccine at fridge temp should be discarded.
Zostavax® [package insert]. Whitehouse Station, NJ: Merck; April 2011.

65. Administration Zostavax: SINGLE 0.65-mL dose (reconstituted)
SQ – upper, outer tricep
5/8 inch, 25 gauge needle

66. What is the maximum length of time between reconstitution and administration of Zostavax?
10 minutes
30 minutes
1 hour
1 day 2

67. Prevention of Zoster and Postherpetic Neuralgia
Shingrix®
(Herpes Zoster Adjuvanted Subunit Vaccine)

68. Coming soon: Shingrix®
Inactivated, recombinant zoster subunit vaccine
Manufactured by GlaxoSmithKline
ADD: table comparing zostavax and shingrix (storage, administration, formulation)
Combines glycoprotein E with an adjuvant system suspension
Adjuvant is bacterial, from salmonella minesota
Also found effective against postherpatic neuralgia (PHN)
Mention: Will likely be an option for immunocomprimised patients and patients ≥50 year olds, Better efficacy and lasting protection compared to Zostavax

69. Storage and Administration
Stored in the refrigerator at 4o C
Suspension that must be reconstituted with adjuvant suspension upon administration
IM injection
2 dose series, given 2-6 months apart

70. Coming soon: Shingrix®
Trials:
ZOE-50: Shingrix reduced risk of herpes zoster by 97.2% in patients year olds
(Zostavax had only 70% efficacy for the same population group)
ZOE-70: Shingrix reduced risk of herpes zoster by 90% in patients ≥70 years old
(Zostavax had only 38% efficacy for the same population group)
Zoster-048: Shingrix demonstrates appropriate immunogeneicity and safety data in all approved populations regardless of if the patient has received a previous Zostavax vaccine
Should patients wait for Shingrix to be approved to get vaccinated?
Patients previously vaccinated with Zostavax may be indicated for a Shingrix booster shot?
Better efficacy → 90-97% depending on age
Offers lasting protection → does not wane over at least 4 years, possibly 9 years
Administration to immunocompromised will be labeled indication

71. Coming soon: Shingrix®
Status:
Recommended for approval by the FDA panel (11-0 vote)
Now up for approval by the FDA at the end of October
Will then be considered at ACIP meeting on Oct. 25 for current guidelines

72. Summary Zostavax Shingrix Formulation Powder for reconstitution
Suspension for reconstitution
Storage
Freezer
Refrigerator
Administration SQ
Single Dose IM
2 doses
Efficacy
38-70%
90-97%
Type
LIVE
INACTIVATED
Comparison table

73. Questions and Discussion