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 2016 including the new quadrivalent and mammalian cell vaccines.
Identify vaccine contraindications and recommend vaccines based upon age and medical history.
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 Immunization Schedule

5. 2017 CDC ACIP Recommendations
HPV
Before age 15: two-dose schedule (five months apart) of nine-valent HPV vaccine (HPV9; Gardasil 9).
After age 15: three-dose schedule of nine-valent HPV vaccine.
Meningitis
A two-dose schedule of meningitis B vaccine (MenB) for adolescents.
However, three doses are recommended in cases of meningitis outbreaks or if a person is at increased risk for contracting the disease.

6. Influenza Vaccines

7. 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. 7

10. ACIP Recommendations 2016-17 Influenza Season
For 2016–17, U.S.-licensed trivalent influenza vaccines contain:
A/California/7/2009 (H1N1)-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 (H3N2) virus and the influenza B virus as compared with the 2015–16 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.
In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013–14 and 2015–16 seasons, for the 2016–17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used.
Persons who report having had reactions to egg involving such symptoms as angio-edema, respiratory distress, lightheadedness, or recurrent emesis; or who required epinephrine or another emergency medical intervention, may receive Flublok if they are aged 18 years or older and there are no other contraindications.

11. Age Indication for Influenza Vaccines: United States, 2016-2017
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+).

12. New Influenza Vaccines:
Fluarix ® (GlaxoSmithKline) – inactivated, quadrivalent vaccine
FDA approved December 2012
People ages 3 years and older
Fluzone® (Sanofi Pasteur) – inactivated, quadrivalent vaccine.
FDA approved March 2013
People ages 6 months and older
Fluad ® (Seqirus) Adjuvanted trivalent inactivated vaccine
FDA approved November, 2015
People ages 65 and older
Flumist® Quadrivalent (MedImmune)– live, attenuated, quadrivalent vaccine
FDA approved March, 2012
People ages 2 through 49 years
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.
People ages 18 years and older
Doesn’t list “severe allergic reaction to egg protein” in the contraindications

13. Which of the following is the predominant flu strain of 2016-17?
Type B strain in trivalent vaccine
Type B strain not in trivalent vaccine
Type A H1N1 strain
Type A H3N2 strain

14. Adjuvanted Trivalent Inactivated Influenza Vaccine Fluad®

15. 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

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

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

18. Seroconversion Rates at Day 22

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

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

21. New Influenza Vaccines:
Fluarix Quadrivalent® (GlaxoSmithKline) – inactivated, quadrivalent vaccine which contains two type A and two type B strains
FDA approved December 2012
People ages 3 years and older
Fluzone Quadrivalent® (Sanofi Pasteur) – inactivated, quadrivalent vaccine which contains two type A and two type B strains
FDA approved March 2013
People ages 6 months and older

22. Quadrivalent vs. Trivalent: Local Side Effects
Fluarix Quadrivalent
N=3,015
Trivalent Influenza Vaccine (TIV)
TIV-1
(B Victoria) N=1,003
TIV-2
(B Yamagata)
N=607
Pain 36 37 31
Redness 2
Swelling 1
Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

23. Quadrivalent vs. Trivalent: Systemic Side effects
Fluarix Quadrivalent
N=3,015
Trivalent Influenza Vaccine (TIV)
TIV-1
(B Victoria) N=1,003
TIV-2
(B Yamagata)
N=607
Muscle Aches 16 19
Headache 13
Fatigue 18 15
Arthralgia 8 10 9
GI Symptoms 7 6
Shivering 4 5
Fever ≥99.5°F 2 1
Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

24. Quadrivalent vs. Placebo: Vaccine Efficacy
Attack Rates (n/N)
Vaccine Efficacy N % LL UL
Antigenically Matched Strains
FLUARIX
5,103 49
1.0
66.9
51.9
77.4
placebo
2,549 74
2.9 -
All Cultured-Confirmed Influenza (Matched, Unmatched, and Untyped) 63
1.2
61.6
46.0
72.8 82
3.2
Fluarix [package insert]. Dresden, Germany: GlaxoSmithKline Inc; 2013.

25. 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%.

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

27. 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

28. Live Attenuated Influenza Vaccine (LAIV) Quadrivalent Flumist®

29. New Influenza Vaccines:
Flumist® Quadrivalent (MedImmune)– live attenuated vaccine which contains two type A and two type B strains
FDA approved March, 2012
People ages 2 through 49 years

30. Live Attenuated Influenza Vaccine
Indication
Healthy people 2 through 49 years of age
Contraindications
Pregnant women
People who have long-term health problems with:
heart disease
kidney or liver disease
lung disease
metabolic disease, such as diabetes
asthma
anemia, and other blood disorders
Anyone with a weakened immune system
Severe egg allergy
I pick my nose!

31. Administration
Flumist®: 0.1-mL dose in each nostril
Intranasal

32. ACIP votes down use of LAIV for 2016-2017 flu season
CDC’s Advisory Committee on Immunization Practices (ACIP) today voted that live attenuated influenza vaccine (LAIV), also known as the “nasal spray” flu vaccine, should not be used during the flu season. ACIP continues to recommend annual flu vaccination, with either the inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV), for everyone 6 months and older.

37. Select the TRUE statement:
ACIP does not recommend LAIV for the influenza season
ACIP continues to recommend annual influenza vaccine for 6 mos and older
LAIV is not recommended due to concerns regarding low effectiveness
All statements are true

38. Pharmajet®

39. According to Pharmajet®…
The surveys revealed that most patients were satisfied with their PharmaJet Needle-Free flu shot experience and were likely to choose the option again. Specifically:
96% were satisfied
92% preferred the PharmaJet Needle-Free flu shot
92% would recommend a PharmaJet Needle-Free flu shot to family and friends

40. McAllister et al_2014_Lancet*

41. McAllister et al_2014_Lancet*
Methods:
Randomized (1:1), open-label trial.
Healthy adults aged years (N = 1250)
Afluria (trivalent inactivated influenza vaccine)
IM needle-free jet injector
IM with needle and syringe
Outcomes:
Antibody titers
Seroconversion rates
Adverse events
Lancet 2014;384:

42. McAllister et al_2014_Lancet*

43. McAllister et al_2014_Lancet*
Seroconversion rates of participants in the
immunogenicity population by study group
McAllister et al_2014_Lancet*
Lancet 2014;384:

44. Lancet 2014;384:

45. Pain Itching Swelling Redness Bruising
Which of the following local side effects is more common when Afluria is administered via Pharmajet versus syringe/needle?
Pain
Itching
Swelling
Redness
Bruising

46. Intradermal Quadrivalent Inactivated Influenza Vaccine (IIV) Fluzone Intradermal®

47. Intradermal Influenza Vaccine
Indicated for persons 18 through 64 years of age
Contraindications
Severe egg allergy
Associated with higher rates of injection site reactions (erythema, induration, swelling, and pruritus, but not pain) than the IM inactivated influenza vaccines
Erythema (>75%)
Induration (>50%)
Swelling (>50%)
Pain (>50%)
Pruritus (>40%)

48. Intradermal vs Traditional IM needle Length

49. 30 Gauge Needle and Less Volume

50. Methods: Multicenter, randomized, double-blind controlled study
ID vaccine (9 mcg of hemagglutinin per strain) N=1,803
IM vaccine (15 mcg of hemagglutinin per strain): N=452
in adults 18 to 60 years of age.
Human Vaccines. 2010;6:

51. Comparison of local side effects to ID and IM influenza vaccine
Percent
Human Vaccines. 2010;6:

52. Intradermal Injection Technique
Remove needle cap
Hold microinjection system
between thumb and middle finger
Do not place fingers on the windows
Insert needle rapidly perpendicular
to the skin
Inject using the index finger
Remove needle from the skin and activate the needle shield by
pushing firmly on the plunger

53. Injection site swelling Malaise
Which side effect is more common with the intradermal influenza vaccine than the IM influenza vaccine?
‘flu’ like symptoms
Headache
Fever
Injection site swelling
Malaise

54. The mother of a 12-year-old child requests the least painful influenza vaccination. What would you recommend this season?
Afluria via Pharmajet
Flumist Nasal Spray
Fluzone Intradermal
Fluzone Intramuscular

55. Tips for an Ouch-Free Flu Shot
Do not prepare the vaccine in front of the patient.
Use a prefilled syringe or change the needle.
Make sure the alcohol is dry before injecting.
Ensure the patient’s arm is relaxed.
Inject into the deltoid at least 3 finger widths below the crest of the shoulder.
Distract kids; ask them to pretend they are blowing out candles on a birthday cake or blow on a pinwheel.
Keep calm and carry on.

56. Inactivated, Trivalent Recombinant Vaccine Flublok®

57. 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.

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

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

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

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

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

63. High-Dose Inactivated Influenza Trivalent Vaccine (IIV) Fluzone HD®

64. Methods: Multicenter, randomized, double-blind controlled study
HD vaccine (60 mcg of hemagglutinin per strain): N=15,991
SD vaccine (15 mcg of hemagglutinin per strain): N=15,998
Adults 65 years and older. Nursing home residents and immunocompromised persons were excluded.
Diazgranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):
N Engl J Med 2014;371:635-45

65. Occurrence of laboratory-confirmed influenza following administration of HD and SD influenza vaccines
Number of cases
Diazgranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):
N Engl J Med 2014;371:635-45

66. Methods: Retrospective cohort study
Lancet Infect Dis 2015;15:
Methods:
Retrospective cohort study
HD vaccine (60 mcg of hemagglutinin per strain): N= 929,730
SD vaccine (15 mcg of hemagglutinin per strain): : N= 1,615,545
US Medicare beneficiaries 65 years and older who received influenza vaccine in a community pharmacy
Primary outcome: probable episode of influenza-related illness defined by a community medical encounter with the provision of a rapid influenza test followed by dispensing of oseltamivir within a 2-day period

67. Efficacy of HD Vaccine versus SD Vaccine Against Influenza-Related Illness
Similar results to Diazgranados et al.
Those who received IIV-HD 22% less likely to have influenza-associated illness and 22% less likely to be admitted to the hospital for influenza
Each plot displays the rate of influenza per person-weeks. Data was smoothed using a weighted average,
placing a weight of 0・5 on the current week and a weight of 0・25 on the previous and following weeks. (A) Rapid
infl uenza test followed by treatment with oseltamivir. (B) Inpatient hospital admissions or emergency department
visits with an infl uenza International Classifi cation of Diseases, ninth revision, Clinical Modifi cation code. RIT=rapid
infl uenza diagnostic test.
Lancet Infect Dis 2015;15:

68. Administration Fluzone HD®: 0.5-mL dose IM - deltoid
1 inch, 25 gauge needle

69. Influenza Vaccines: Summary

70. Age Indication for Influenza Vaccines: United States, 2016-2017
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+).

71. Characteristics of Influenza Vaccines: United States, 2016-17
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.

72. Route of Admin. for Influenza Vaccines: United States, 2016-17
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.

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

74. 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

75. 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.

77. ACIP Recommendations on Pneumococcal Vaccinations in Adults

78. 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.

79. 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.

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

81. 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

82. Same day, opposite arm, separate syringe
Which of the following statements about the administration of influenza and pneumonia vaccines is true?
Same day, opposite arm, separate syringe
Same day, same arm, mixed in 1 syringe
Must be separated by at least 7 days
Must be separated by at least 4 weeks

83. Questions and Discussion