1. Vaccination of Adolescents: New Frontiers Andrew Kroger National Center for Immunization and Respiratory Diseases National Assembly on School- based Health Care (NASBHC) May 16, 2007

2. Vaccine Research and Development Basic research, animal studies Phase I: safety, Immunogenicity(10-20) Phase II: Dose ranging (20- several hundred) Phase III: safety, efficacy (several hundred to several thousand) Biologics License Application

3. Vaccines of the Future Cytomegalovirus Human immunodeficiency virus Herpes simplex virus Group B streptococcus

4. Challenges to New Vaccine Development Understanding the immune response to natural infection not complete Humoral and cell-based immune response important to developing an effective vaccine Need to be able to test efficacy – often outcomes difficult to study due to long latency

5. Cytomegalovirus Herpesvirus Latent virus with reactivation Infection is Common Congenital CMV Severe in patients with Altered Immunocompetence

6. CMV Vaccines Candidates Live-attenuated and subunit vaccines (Phase I) Vector vaccines (canarypox virus vector) Challenges Humoral and cellular response critical

7. Human Immunodeficiency Virus (HIV) Infection 1 million infected in U.S. 25% unaware of their infection Progresses to Acquired Immunodeficiency Syndrome (AIDS) HIV virus transmission – sexual and percutaneous HIV pathogenesis per- cutaneous and mucosal route

8. HIV Vaccine Trials Network 56 trials occurring in 25 sites worldwide 29 candidate vaccines Strategies Recombinant vectors Prime-boost approach

9. HIV Vaccines Challenges Effective animal models for preclinical trials Determining appropriate outcomes to measure

10. Herpes simplex virus (HSV) Family Herpesvirus Reactivation disease HSV1: Cold sores HSV2: Genital herpes

11. HSV Vaccine candidates Subunit vaccine (phase II): efficacy in women Live attenuated (current phase I) Challenges Determining efficacy

12. Group B Streptococcus Perinatal transmission Asymptomatic colonization (21% pregnant women) Causes sepsis in newborns Generally treated with antibiotics during labor

13. GBS Vaccines Pure polysaccharide Protein conjugate vaccines (phases I, II) Challenges Multiple serotypes

18. Link to the Jordan Report from NIP website

19. Vaccine-preventable diseases and adolescents: why so many cases?

20. Pertussis

21. Pertussis Impact Among Adolescents & Adults Pneumonia (2%) Rib fractures (1%) Hospitalization (~1%) Medical costs Missed school and work Impact on public health system Loss of sleep; loss of consciousness Weight loss

22. Why Adolescents & Adults need Pertussis Vaccine In 2003 pertussis vaccine levels in children 19-35 months highest ever Pertussis cases continued to rise 2005 – 25,616 pertussis cases, highest recorded since 1959 –67% of cases - adolescent or adult –Overall incidence is 8.7/100,000 –Infants < 6 months 160.8/100,000 Pertussis immunity wanes in 5-10 years

23. Pertussis Trends in the U.S. 1994-2004 reported cases, 5x higher 2001-2005* - 109 pertussis-related deaths 88/109 or >80% who died were too young to have completed a primary series of DTaP Source of infection most often an older child or adult in the household *2001-15; 2002-22; 2003-18; 2004-16; 2005-38 CDC unpublished data

24. Why Pertussis in Adolescents? Waning immunity Improved diagnostics Improved surveillance

25. Tdap Vaccine Tdap vaccines licensed by FDA May and June 2005 ACIP Recommendations for adolescents in MMWR March 2006 ACIP Recommendations for adults in MMWR December 2006

26. Pertussis Vaccines - Tdap Boostrix ® (GlaxoSmithKline) –Licensed May 3, 2005 –Single dose –Approved for persons 10-18 years of age Adacel ® (sanofi pasteur) –Licensed June 10, 2005 –Single dose –Approved for persons 11-64 years of age

27. Adolescent-Adult Pertussis Vaccination ObjectivesPrimary – Protect vaccinated adolescents – Continue protection after completion of initial series Secondary – Reduce B. pertussis reservoir – Reduce pertussis incidence in other age groups

28. General Principles Use of Tdap and Td Tdap is preferred for protection against pertussis Tdap is licensed for ONE single dose at this time

29. Tdap Adolescent Recommendations Adolescents 11-12 years of age should receive a single dose of Tdap instead of Td* Adolescents 13-18 years with no Tdap should receive one dose as a catch-up booster instead of Td* *if the person has completed the recommended childhood DTaP vaccination series, and has not yet received a Td booster

30. Persons >10 years with NO History of Primary Series Use 3 dose adult schedule but give Tdap for first dose of series Preferred schedule – #1 Tdap – #2 Td – at least 4 wks after dose #1 – #3 Td – at least 6 mos after dose #2

31. Tdap Recommended Uses Persons >10 yrs and adults who anticipate or have close contact with infants <12 months of age should receive one dose of Tdap Tdap can be used for tetanus prophylaxis wound management Use Tdap for next routine booster dose even if history of pertussis disease HCP with direct patient contact, esp. if <12 months age. Interval can be 2 years

32. Tdap Uses in Pregnancy* Safety data not available; registry is in progress If tetanus and diphtheria protection needed, give Td If pertussis risk present, give Tdap Pertussis risk in pregnancy = adolescents, pregnant HCP, child care providers of infants <12 months or vulnerable persons, living or working in area with increased pertussis Td and Tdap when vaccine should not be deferred to post partum, administration in 2 nd or 3 rd trimester is preferred *See section 3-K in Adolescent Tdap ACIP Recommendations

33. Schoeller T, Schmutzhard E. N Engl J Med. 2001;344:1372 Schoeller T, Schmutzhard E. N Engl J Med. 2001;344:1372 Meningococcal Disease

34. Rates of Meningococcal Disease* by Age, 11-30 y/o, United States, 1991-2002 * Serogroups * Serogroups A/C/Y/W135 U.S. Rate

35. Risk Factors for Meningococcal Disease in the United States Deficiencies in the terminal complement pathway Functional or anatomic asplenia HIV infection Smoking Passive exposure to smoke Upper respiratory tract infection Crowding

37. 18-23 years old1.4 / 100,000 18-23 years old not college student1.4 / 100,000 Freshmen1.9 / 100,000 Freshmen in dorm5.1 / 100,000 18-23 years old1.4 / 100,000 18-23 years old not college student1.4 / 100,000 Freshmen1.9 / 100,000 Freshmen in dorm5.1 / 100,000 Meningococcal Disease Among Young Adults, United States, 1998-1999 Bruce et al, JAMA 2001;286;688- 93

38. Approved by FDA January 2005

39. Menactra TM (sanofi pasteur) Quadrivalent (serogroups A, C, Y, W-135) conjugated to diphtheria toxoid Approved for persons 11-55 years of age Schedule: 1 dose Administered by intramuscular injection Meningococcal Conjugate Vaccine

40. Approved only for persons 11 through 55 years of age Persons 2-10 years of age >55 years at increased risk should receive the meningococcal POLYSACCHARIDE vaccine Meningococcal vaccine is not routinely recommended for persons 2-10 years of age or older than 55 years who are not in a high risk group

41. Meningococcal Vaccine Recommendations Recommended for: –all persons at the preadolescent visit (ages 11- 12 years) –persons about to enter high school (age 15 years) –college freshmen living in a dormitory –other adolescents who wish to reduce their risk for meningococcal disease MMWR 2005;54(RR-7)

42. Meningococcal Vaccine Recommendations Recommended for certain high-risk persons: –military recruits –certain research and laboratory personnel –travelers to and U.S. citizens residing in countries in which N. meningitidis is hyperendemic or epidemicterminal complement component deficiency –functional or anatomic asplenia –HIV infection (“should be considered”) MMWR 2005; 54(RR-7);1-21

44. Meningococcal Conjugate Vaccine (MCV) and GBS MCV approved by FDA in January 2005 15 cases of GBS among 11-19 year olds within 6 weeks of MCV FDA/CDC advisory issued September 30, 2005 No change in vaccine recommendations as of October 20, 2005* *except to avoid vaccination of persons with a history of GBS who are not at increased risk of infection

45. Newsweek: 1 May 2006 Dubuque, Iowa 1956 Philadelphia

46. Why Mumps in Adolescents? Highly communicable Imperfect vaccine efficacy

47. 70-80% after one dose 90-95% after two doses Therefore: 50-100 of 1,000 immunized persons will be infected Of 100 people, 98 are immunized  5 or 5% of the 98 get mumps  2 unvaccinated get mumps  5 of the 7 total who get mumps will be immunized Mumps Vaccine Efficacy

48. Mumps Prevention Immunization –TWO doses for school age children –Ensure adult immunity –Healthcare workers need immunity!! HCWs need TWO doses MMR or proof of immunity Identify and isolate ill persons for ~ 9 days –note location, date for epi-link Identify and vaccinate susceptible contacts Practice good hygiene

49. Adolescent Vaccination

51. Questions?