1. Kenneth McCall, BSPharm, PharmD 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 2015-16 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 influenza and pneumonia vaccines.

3. Outline Background & Principles of Vaccination Regulations Influenza Vaccines Pneumococcal Vaccines HPV9 Vaccine

5. ACIP Recommended Adult Immunization Schedule, by vaccine and age group www.cdc.gov/vaccines/schedules/hcp/adult.html

6. Vaccines that might be indicated for adults based on medical and other indications www.cdc.gov/vaccines/schedules/hcp/adult.html

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11. ACIP Recommendations 2015-16 Influenza Season For 2015–16, U.S.-licensed trivalent influenza vaccines will contain the A/California/7/2009 (H1N1)-like virus, an A/Switzerland/9715293/2013 (H3N2)- like virus, and a B/Phuket/3073/2013-like (Yamagata lineage) virus. This represents changes in the influenza A (H3N2) virus and the influenza B virus as compared with the 2014–15 season. Quadrivalent influenza vaccines will contain these vaccine viruses, and a B/Brisbane/60/2008-like (Victoria lineage) virus. All persons aged ≥6 months should receive influenza vaccine annually. Persons who care for severely immunosuppressed persons who require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus. 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. MMWR August 7, 2015 / 64(30);818-825

13. Egg Allergy Recommendation MMWR August 7, 2015 / 64(30);818-825

14. 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 Flumist® Quadrivalent (MedImmune)– live, attenuated, quadrivalent vaccine FDA approved March, 2012 People ages 2 through 49 years Flucelvax® (Novartis)– trivalent inactivated vaccine grown in mammalian cells. FDA approved November, 2012 Adults 18 years and older Doesn’t list “severe allergic reaction to egg protein” in the contraindications 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 Fluzone Intradermal Quadrivalent (Sanofi)-inactivated, quadrivalent vaccine FDA approved January, 2015 Adults 18 to 64 years of age

15. Age Indication for Influenza Vaccines: United States, 2015-16 Vaccine0.5-2 years 2 years 3 years 4-8 years 9-17 years 18-49 years 50-64 years 65+ years Fluzone / Fluzone Quad ✓✓✓✓✓✓✓✓ Flumist Quad ✓✓✓✓✓ Fluarix Quad ✓✓✓✓✓✓ FluLaval Quad ✓✓✓✓✓✓ Fluvirin ✓✓✓✓✓ Afluria 1 ✓✓✓✓ Flucelvax ✓✓✓ Flublok 2 ✓✓✓ Fluzone Intradermal Quad ✓✓ Fluzone High-Dose ✓ 1.Age indication per package insert is >5 years; however the ACIP recommends >9 years. 2.FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+).

16. Which strain is the predominant flu strain so far this year? 1. Type B strain in trivalent vaccine 2. Type B strain not in trivalent vaccine 3. Type A H1N1 strain 4. Type A H3N2 strain

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18. 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

19. Quadrivalent Influenza Vaccines contain which of the following? 1. Four type A strains 2. Two type A strains, 1 type B, & 1 type C 3. Two type A strains & 2 type B strains 4. Four type B strains

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21. 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

22. 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 22 I pick my nose!

23. Administration Flumist®: 0.1-mL dose in each nostril Intranasal 23

24. Which of the following patients is a candidate for the live influenza vaccine? 1. 45 yo man with severe egg allergy 2. 27 yo healthy woman 3. 38 yo man with diabetes 4. 54 yo healthy man 5. 19 yo pregnant woman

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26. New Influenza Vaccines: Flucelvax® (Novartis)– trivalent inactivated vaccine grown in mammalian cells rather than chicken embryo cells. FDA approved November, 2012 Adults 18 years and older Doesn’t list “severe allergic reaction to egg protein” in the contraindications

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28. 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 18-49 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.

29. Select an influenza vaccine for a healthy 37- year-old woman with severe egg allergy. 1. Flublok 2. Flumist 3. Fluzone 4. Fluarix

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31. 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. 31 N Engl J Med 2014;371:635-45

32. DiazGranados_2014_NEJM How well does the study design limit bias? Who was enrolled in the study/who does the study apply to? What is the primary outcome and is the result statistically significant? Is the result clinically significant? What is the benefit/risk?

33. Occurrence of laboratory-confirmed influenza following administration of HD and SD influenza vaccines 33 Number of cases N Engl J Med 2014;371:635-45

34. Efficacy of HD Vaccine vs. Standard Dose against Laboratory Confirmed Influenza of Any Type Number (%) of cases IV3-HD: 228/15,990 (1.4%) IV3-SD: 301/15,993 (1.9%) Relative Efficacy (95% CI) 24.2% (9.7% – 36.5%) Absolute Efficacy 0.5% Number Needed to Treat 200

35. Which of the following statements is FALSE when comparing the efficacy of Fluzone HD to Fluzone in adults 65 years or older? 1. The relative efficacy of Fluzone HD is 24% > than Fluzone 2. The absolute efficacy of Fluzone HD is 0.5% > than Fluzone 3. These results apply to nursing home patients 4. The NNT is 200 to avoid one additional case of influenza

37. Intradermal Influenza Vaccine Indication Persons 18 through 64 years of age Contraindications Severe egg allergy 37

38. Intradermal vs Traditional IM needle Length

39. 30 Gauge Needle and Less Volume

40. Intradermal Injection Technique 1. Remove needle cap 2. Hold microinjection system between thumb and middle finger  Do not place fingers on the windows 3. Insert needle rapidly perpendicular to the skin 4. Inject using the index finger 5. Remove needle from the skin and activate the needle shield by pushing firmly on the plunger

41. Which side effect is more common with the intradermal influenza vaccine than the IM influenza vaccine? 1. Injection site pain 2. Headache 3. Fever 4. Injection site swelling 5. Malaise

43. Age Indication for Influenza Vaccines: United States, 2015-16 Vaccine0.5-2 years 2 years 3 years 4-8 years 9-17 years 18-49 years 50-64 years 65+ years Fluzone / Fluzone Quad ✓✓✓✓✓✓✓✓ Flumist Quad ✓✓✓✓✓ Fluarix Quad ✓✓✓✓✓✓ FluLaval Quad ✓✓✓✓✓✓ Fluvirin ✓✓✓✓✓ Afluria 1 ✓✓✓✓ Flucelvax ✓✓✓ Flublok 2 ✓✓✓ Fluzone Intradermal Quad 3 ✓✓ Fluzone High-Dose ✓ 1.Age indication per package insert is >5 years; however the ACIP recommends >9 years. 2.FDA labeled age indication expanded in 2015 to 18 years and older (now including adults 65+). 3.Reformulated to Quadrivalent in 2015.

44. Characteristics of Influenza Vaccines: United States, 2015-16 VaccineLiveMercuryEgg Protein Latex Fluzone / Fluzone Quad ✓1✓1 ✓ Flumist Quad ✓✓ Fluarix Quad ✓ FluLaval Quad ✓✓ Fluvirin ✓1✓1 ✓✓3✓3 Afluria ✓1✓1 ✓ Flucelvax ✓2✓2 ✓3✓3 Flublok Fluzone Intradermal Quad ✓ Fluzone High-Dose ✓ 1.Multi-dose vials contain mercury. Single-dose prefilled syringes are mercury-free. 2.Estimated to contain <50 femtograms (5x10 -8 mcg) of total egg protein per 0.5 ml dose. 3.Syringe tip may contain natural rubber latex.

45. Route of Admin. for Influenza Vaccines: United States, 2015-16 VaccineYoung Children* Older Children Adults Fluzone / Fluzone Quad IM ThighIM Deltoid Flumist Quad Intranasal Fluarix Quad IM ThighIM Deltoid FluLaval Quad IM ThighIM Deltoid Fluvirin IM ThighIM Deltoid Afluria IM Deltoid Flucelvax IM Deltoid Flublok IM Deltoid Fluzone Intradermal Quad ID Deltoid Fluzone High-Dose IM Deltoid *Generally, less than 7 years old.

48. Background Streptococcus pneumoniae 90 serotypes identified The 10 most common serotypes are estimated to account for about 62% of invasive disease worldwide Up to 36% of adult CAP Up to 50% of HAP 13-19% of all cases of meningitis CDC: Vaccines and Immunizations. Pneumococcal Disease. http://www.cdc.gov/. Accessed 30 July 2014.http://www.cdc.gov/

49. Pneumococcal Vaccines Pneumovax 23® (PPSV23, pneumococcal polysaccharide vaccine) Prevnar 13® (PCV13, pneumococcal conjugate vaccine)

51. PPSV23 (Pneumovax®) AgeWho receives the vaccine? ≥65 years old (See figure 1 on next slide) Vaccination history unclear or never received vaccine before Revaccinate: If patient received vaccine before the age of 65 and it has been ≥ 5 years since administration 2-64 years old Chronic cardiovascular disease (CHF, cardiomyopathies) Chronic pulmonary disease (COPD) Diabetes mellitus Alcoholism Chronic liver disease Cerebrospinal fluid leaks Re-vaccination after 5 years if: (see figure 1 on next slide) functional or anatomic asplenia Immunocompromising conditions Chronic kidney disease 19-64 years old Cigarette smokers Asthma ACIP: Pneumococcal. MMWR. http://www.immunize.org/acip/ Accessed 30 July 2014.http://www.immunize.org/acip/

52. ACIP Recommendations on Pneumococcal Vaccinations in Adults

53. 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.

54. 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.

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

56. Methods: Multicenter, randomized, double-blind controlled study PCV13 Vaccine: N=42,240 Placebo: N=42,256 Adults 65 years and older. Nursing home residents and immunocompromised persons were excluded. 56 N Engl J Med 2015;372:1114-1125

57. Bonten_2015_NEJM How well does the study design limit bias? Who was enrolled in the study/who does the study apply to? What is the primary outcome and is the result statistically significant? Is the result clinically significant? What is the benefit/risk?

58. Analysis of the Cumulative Episodes of Vaccine-Type CAP in the Per-Protocol Population N Engl J Med 2015;372:1114-1125

59. Efficacy of PCV13 vs Placebo: First episode of confirmed CAP (Per Protocol) Number (%) of cases PCV13: 49/42,240 (x.x%) Placebo: 90/42,256 (x.x%) Relative Efficacy (95% CI) 45.6% (21.8% – 62.5%), p<0.001 Absolute Efficacy Number Needed to Treat

60. A 67-year-old woman has a history of type 2 diabetes. No prior pneumonia vaccination. What pneumonia vaccine(s) is/are recommended? 1. Pneumovax only 2. Prevnar only 3. Both; Pneumovax prior to Prevnar 4. Both; Prevnar prior to Pneumovax