1. 2016 Adult Immunization Update. David H
2016 Adult Immunization Update David H. Spach, MD Professor of Medicine Division of Infectious Diseases University of Washington, Seattle Y Y Y Y Y Y Y Y Y 1

2. Adult Immunization Update
Conjugate Vaccine Concept
Pertussis Vaccine
Influenza Vaccine
Zoster Vaccine
Pneumococcal Vaccine
Rabies Vaccine 1

3. Vaccine Types: Polysaccharide
Mature B-Cell 1

4. Vaccine Types: Polysaccharide
Mature B-Cell
Activated B-Cell 1

5. Vaccine Types: Polysaccharide
T-Cell Independent Shorter-Term Immunity Lack of Anamnestic Response
Polysaccharide Y Y Y Y Y Y Y Y
Antibodies
Mature B-Cell
Activated B-Cell 1

6. Vaccine Types: Conjugate
Polysaccharide-Protein Conjugate
Antigen Presenting Cell
Interleukins 4, 5, and 6
Activated T-Cell
Th2 Cell 1

7. Vaccine Types: Conjugate
Polysaccharide-Protein Conjugate
B Cell 1

8. Vaccine Types: Conjugate
Polysaccharide-Protein Conjugate
B Cell
Antigen Presenting Cell
Th2 Cell 1

9. Vaccine Types: Conjugate
Polysaccharide-Protein Conjugate
B Cell
Antigen Presenting Cell
Activated T-Cell
Th2 Cell Y Y Y Y Y Y Y Y
Memory B Cell
Plasma Cell
IgG Antibodies 1

10. Vaccine Types: Conjugate
T-Cell Dependent Longer-Term Immunity Good Anamnestic Response Good Response in Young Children
Polysaccharide-Protein Conjugate
B Cell
Antigen Presenting Cell
Activated T-Cell
Th2 Cell Y Y Y Y Y Y Y Y
Memory B Cell
Plasma Cell
IgG Antibodies 1

11. Where do you find out what vaccines are recommended and information about new vaccines?1

12. Advisory Committee on Immunization Practices (ACIP) 2016 Recommended Adult Immunization Schedule
Source: ACIP. MMWR Morb Mortal Wkly Rep. 2016;65(4):88-90. 1

13. ACIP 2016 Recommended Adult Immunization Schedule Vaccinations Indicated Based on Medical or Other Indications
Source: ACIP. MMWR Morb Mortal Wkly Rep. 2016;65(4):88-90. 1

14. Pertussis Vaccine 1

15. Reported Pertussis Cases in U.S. 1922-2014
Source: CDC and Prevention. National Notifiable Disease Surveillance System. 1

16. Reported Pertussis Incidence by Age Group 1990-2014
Source: CDC and Prevention. National Notifiable Disease Surveillance System. 1

17. 2014: Pertussis Epidemiology in U.S.
32,971 cases
13 deaths
Incidence/100,00 highest in age < 1
Number of cases highest in age 11-19
Washington State: 861 cases
Source: CDC and Prevention Pertussis Surveillance Report. 1

18. Case 1
A 67-year-old man comes into the ER with a laceration on his hand that he suffered while working on his house. He has not had a tetanus shot for about 20 years.
What would you recommend regarding a “tetanus shot”? A. No need for vaccine since he is older than 65 and has immunity B. Give Td vaccine now and repeat Td in about 10 years C. Give Tdap now and give Td in about 10 years D. Give Tdap now and repeat Tdap in about 10 years 1

19. Case 2
A 27-year-old woman is seen at her OB-GYN office after recently discovering she was pregnant. Her last menstrual period was 10 weeks prior. She received a Tdap vaccine about 2 years ago when was pregnant.
What would you recommend regarding Tdap? A. Give her tetanus-diphtheria (Td) vaccine in about 8 years B. Give her Tdap in about 8 years C. Give her Tdap now D. Give her Tdap at week during pregnancy 1

20. Substitute 1-Dose of Tdap then 1-Dose Td Booster Every 10 Years
2016 ACIP Recommendations for Adults Tetanus, Diphtheria, & Acellular Pertussis Vaccination (Td/Tdap)
Age Groups (Years)
19-49
50-64
65 and Older
Substitute 1-Dose of Tdap then 1-Dose Td Booster Every 10 Years
Pregnant women should receive Tdap with each pregnancy (at weeks of gestation) regardless of interval since prior Td or Tdap vaccination
Source: ACIP. MMWR Morb Mortal Wkly Rep. 2016;65(4):88-90. 1

21. Seasonal Influenza Vaccine1

22. Influenza Viruses Hemagglutinin “H” Neuraminidase “N” RNA
M2 protein (only on type A) 1

23. Influenza Vaccine: Question 1
What is the most important new recommendation for the influenza vaccine for the season? 1

24. Live Attenuated Influenza Vaccine (LAIV)X
Source: ACIP. June 22, 2016. 1

25. “In late May, preliminary data on the effectiveness of LAIV among children 2 years through 17 years during season became available from the U.S. Influenza Vaccine Effectiveness Network. That data showed the estimate for LAIV vaccine effectiveness among study participants in that age group against any flu virus was 3 percent.”
Source: ACIP. June 22, 2016.
LAIV = Live Attenuated Influenza Vaccine 1

26. Influenza Strains in US 2016-2017 Influenza Vaccine*
A/California
A/Hong Kong
B/Brisbane
*B/Phuket
*Available in the quadrivalent influenza vaccines
Source: CDC and Prevention. 1

27. Newer Influenza Vaccines
High-Dose Influenza Vaccine (Fluzone High Dose) - FDA approved in 2009 for persons ≥65 years of age - Contains 4x influenza antigen
Cell-Based Influenza Vaccine (Flucelvax) - FDA approved in Uses egg-grown virus, mixed with cultured mammalian cells
Recombinant Influenza Vaccine (Flublok) - FDA-approved in Use hemagluttinin protein; does not use eggs at any stage 1

28. Influenza Vaccine: Question 2
Should Persons 65 and Older Receive High-Dose or Standard-Dose Influenza Vaccine? 1

29. Should Persons 65 and Older Receive High-Dose or Standard-Dose Influenza Vaccine?
“At this time, CDC and its Advisory Committee on Immunization Practices have not expressed a preference for either vaccine for people 65 and older, however, there are ongoing studies looking into this issue and new findings will be considered in ACIP's future policy deliberations.”
Source: CDC and Prevention. 1

30. Zoster Vaccine 1

31. “Approximately 1 million new cases of zoster occur in the United States annually.”
“Approximately one in three persons in the general population will develop zoster during their lifetime.”
From: ACIP & Centers for Disease Control. MMWR ;57:1-32. 1

32. Incidence of Zoster and PHN Increases with Age
Source: CDC. MMWR. 2008;57 (05):1-30. 1

33. Incidence of Zoster is Increasing in US
Source: Hales CM, et al. Ann Intern Med. 2013;159: 1

34. Zoster Vaccine in Adults 60 and Older Shingles Prevention Study
Study Design
Zoster and Post Herpetic Neuralgia*
Background - N = 38, Adults aged > Randomized, double-blinded - Excluded those with prior h/o zoster - Followed median of 3.1 years
Vaccines (single dose) - Zoster Vaccine (n = 19,270) - Placebo (n = 19,276)
P < 0.001
P < 0.001
*Zoster Vaccine = Live attenuated Oka
*Effectiveness of Zoster Vaccine - Decreased Herpes Zoster by 51.3% - Decreased PHN by 66.5%
From: Oxman MN, et al. N Engl J Med 2005;352: 1

35. Zoster Vaccine in Adults 50-59 Zoster Efficacy and Safety (ZEST) Trial: protocol 022
Study Design
Efficacy Summary*
Background - N = 22, Adults aged Randomized, double-blinded - Excluded those with prior h/o zoster - Followed median of 1.3 years
Vaccines (single dose) - Zoster Vaccine (n = 11,211) - Placebo (n = 11,228)
*Zoster Vaccine = Live attenuated Oka
*Effectiveness of Zoster Vaccine - Decreased Herpes Zoster by 69.8% - Decreased zoster pain severity-by-duration score by 73%
From: Zostvax Product Information. Merck 1

36. Zoster Vaccine: Question
Who should receive the zoster vaccine? 1

37. Zoster Vaccine (Zostavax)
Vaccine - Live, high-titer, attenuated vaccine (Oka)
FDA-Approval Status - Approved for person age 50 and older regardless of whether they report a prior history of herpes zoster
ACIP Recommendations - Recommended for persons age 60 and older regardless of whether they report a prior history of herpes zoster
Contraindications - History of primary or acquired immunodeficiency states - On major immunosuppressive therapy - Pregnant women
From: ACIP & Centers for Disease Control. 1

38. Use of Zoster Vaccine in Immunocompromised Persons
High dose corticosteroids (> 20 mg/d) for > 14 days - Contraindicated and defer vaccine for > 1 month after corticosteroids stopped
Low dose immunosuppresants: methotrexate (<0.4 mg/Kg/week), azathioprine (<3.0 mg/Kg/day), or 6­ mercaptopurine (<1.5 mg/Kg/day) - NOT contraindicated
Stem Cell Transplantation - Limited experience and take on case-by-case basis
Immune modulators (eg. adalimumab, infliximab, and etanercept) - Case-by-case basis (consider deferring for 1 month after stopping modulator)
From: ACIP & Centers for Disease Control. MMWR ;57:1-32. 1

39. Zoster Vaccines Zostavax Live Attenuated Vaccine
VZV
VZV
Varicella-Zoster Virus
Zostavax Live Attenuated Vaccine
Shingrex Subunit (Glycoprotein E) Vaccine
Investigational 1

40. Investigational
HZ/su (Shingrix) Efficacy Against First Episode of Zoster in Immunocompetent Patients (ZOE-50)
Background - Randomized, Controlled, Phase 3 trial Adults aged > 50; N = 15, Safety and efficacy of herpes zoster subunit (HZ/su) vaccine - Excluded those with prior h/o zoster or immunosuppressed Excluded if previously vaccinated against varicella or zoster
Study Arms (two doses one month apart) - Zoster Subunit Vaccine (n = 7,698) - Placebo (n = 7,713)
Source: Lal H, et al. N Eng J Med. 2015;372: 1

41. Investigational
HZ/su (Shingrix) Efficacy Against First Episode of Zoster in Immunocompetent Patients (ZOE-50)
Source: Lal H, et al. N Eng J Med. 2015;372: 1

42. HZ/su (Shingrix) Vaccine Program
Investigational
HZ/su (Shingrix) Vaccine Program
Study
Population
Objectives
Results/Status
Pivotal Studies
006 (ZOE-50)
Adults ≥50
HZ efficacy, safety
97% effective
022 (ZOE-70)
Adults ≥70
HZ efficacy, safety;
PHN efficacy (pooled 006/022 analysis)
90% effective
002
Adults; *aHSCT
Ongoing
*aHCST = autologous hematopoietic stem cell transplant 1

43. Pneumococcal Vaccines1

44. Streptococcus pneumoniae
Polysaccharide Capsule
Cell Wall
Cell Membrane
DHS/PP 1

45. Pneumococcal Polysaccharide Vaccine (PPSV)
Polysaccharide Capsule
Polysaccharide
Cell Wall
Streptococcus pneumoniae
Cell Membrane
T-Cell Independent Shorter-Term Immunity Lack of Anamnestic Response 1

46. Pneumococcal Conjugate Vaccine (PCV)
Polysaccharide
Protein Conjugate
Polysaccharide Capsule
Cell Wall
Streptococcus pneumoniae
Cell Membrane
T-Cell Dependent Longer-Term Immunity Good Anamnestic Response 1

47. Pneumococcal Vaccines
Trade Name
Pneumococcal Polysaccharide Vaccine (PPV23)
Pneumovax
Pneumococcal Conjugate Vaccine (PCV7)
Prevnar 7
Pneumococcal Conjugate Vaccine (PCV13)
Prevnar 13 1

48. Invasive Pneumococcal Disease among Children ≤5, 1998-2015
All IPD PCV13 types
IPD = Invasive Pneumococcal Disease
Source: CDC. Active Bacterial Core Surveillance Data, Unpublished data. 1

49. Invasive Pneumococcal Disease among Adults ≥65, 1998-2015
All IPD PPSV23 types PCV13 types
IPD = Invasive Pneumococcal Disease
Source: CDC. Active Bacterial Core Surveillance Data, Unpublished data. 1

50. Invasive Pneumococcal Disease among Adults 19-64, 1998-2015
All IPD PPSV23 types PCV13 types
IPD = Invasive Pneumococcal Disease
Source: CDC. Active Bacterial Core Surveillance Data, Unpublished data. 1

51. Pneumococcal Vaccine: Question
A 65-year-old woman is seen for routine visit. She has hypercholesterolemia, but otherwise is in good health. She has never received a pneumococcal vaccine.
What would you recommend regarding pneumococcal vaccine? A. No pneumococcal vaccine is indicated B. Vaccinate now with PPSV-23 and and repeat again after 5 years C. Vaccinate now with PPSV-23 and and repeat again after 5 years D. Vaccinate now with PCV-13, then give PPSV-23 in 1 year and 1

52. Pneumococcal Immunization in Person ≥65 Years of Age
Pneumococcal Vaccine-Naïve
≥ 1 Year
PCV13
PPSV23
Age 65
Source: ACIP. Recommended Adult Immunization Schedule 1

53. Pneumococcal Immunization in Person ≥65 Years of Age
Pneumococcal Vaccine-Naïve
≥ 1 Year
PCV13
PPSV23
Has Already Received PPSV After Age 65
≥ 1 Year
PPSV23
PCV13
Received
Age 65
Source: ACIP. Recommended Adult Immunization Schedule 1

54. Pneumococcal Immunization in Person ≥65 Years of Age
Pneumococcal Vaccine-Naïve
≥ 1 Year
PCV13
PPSV23
Has Already Received PPSV After Age 65
≥ 1 Year
PPSV23
PCV13
Received
Has Received Pneumococcal Polyasaccharide Vaccine Before Age 65
≥ 1 Year
≥ 1 Year
PPSV23
PCV13
PPSV23
Received
≥ 5 years
Age 65
Source: ACIP. Recommended Adult Immunization Schedule 1

55. Pneumococcal Vaccines Key ACIP Recommendations
PCV13 recommended for: - Persons 65 or older - Immunocompromising conditions - HIV infection - Chronic renal failure
When both PCV13 and PPSV23 indicated, give PCV13 first
Maximum number of PPSV23 doses is 3
Give PPSV23 only once for person age 65 or older
Source: CDC and Prevention. MMWR. 2012:61:816-9. 1

56. Pneumococcal Vaccines Key ACIP Recommended Intervals
For immunocompetent adults ≥65, the interval between PCV13 and PPSV23 should be ≥1 year
For Immunocompromised adults ≥18, or adults with anatomical of functional asplenia, cerebrospinal fluid leak or cochlear implants, the interval for PSV13 followed by PPSV23 should be ≥8 weeks
The interval between PPSV23 doses is 5 years
Source: CDC and Prevention. MMWR. 2012:61:816-9. 1

57. Rabies Vaccine 1

58. Case History: Question
A 29-year-old male is bitten on the shoulder by a bat and the bat escaped.
What percent of Rabies Immune Globulin should be given at the wound site? A. 25% B. 50% C. 75% D. 100% 1

59. Case History: Question
In addition to giving Rabies Immune Globulin, how many doses of rabies vaccine should be given? He has never received rabies vaccine before. A. One B. Two C. Four D. Five 1

60. Rabies: Post-Exposure Prophylaxis
Not Previously Vaccinated
Wound cleansing
*Rabies Immune Globulin
+Rabies Vaccine: day 0,3,7,14
*Administer vaccine as IM in deltoid +Administer full dose of RIG around wound if possible; remaining volume give at site distant from vaccine site
*Note: Number of recommended doses of rabies vaccine changed from 5 to 4 (ACIP June 24, 2009)
From: CDC. MMWR 2010;59(RR02):1-9. 1

61. Questions? 1