Vaccination of Adolescents: New

Frontiers

Andrew KrogerNational Center for Immunization and

Respiratory Diseases

National Assembly on School-based Health Care (NASBHC)

May 16, 2007

Vaccine Research and Development

Basic research, animal studiesPhase I: safety,

Immunogenicity(10-20)Phase II: Dose ranging (20-

several hundred)Phase III: safety, efficacy

(several hundred to several thousand)

Biologics License Application

Vaccines of the Future

CytomegalovirusHuman immunodeficiency virus

Herpes simplex virusGroup B streptococcus

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

Cytomegalovirus

HerpesvirusLatent virus with reactivationInfection is Common Congenital CMVSevere in patients with Altered Immunocompetence

CMV Vaccines

Candidates• Live-attenuated and subunit

vaccines (Phase I)• Vector vaccines (canarypox

virus vector)Challenges• Humoral and cellular

response critical

Human Immunodeficiency Virus (HIV) Infection

1 million infected in U.S.25% unaware of their infectionProgresses to Acquired

Immunodeficiency Syndrome (AIDS)

HIV virus transmission – sexual and percutaneous

HIV pathogenesis per-cutaneous and mucosal route

HIV Vaccine Trials Network

56 trials occurring in 25 sites worldwide

29 candidate vaccinesStrategies•Recombinant vectors•Prime-boost approach

HIV Vaccines

Challenges•Effective animal models for preclinical trials

•Determining appropriate outcomes to measure

Herpes simplex virus (HSV)

Family HerpesvirusReactivation disease HSV1: Cold soresHSV2: Genital herpes

HSV

Vaccine candidates•Subunit vaccine (phase II): efficacy in women

•Live attenuated (current phase I)

Challenges•Determining efficacy

Group B Streptococcus

Perinatal transmission

Asymptomatic colonization (21% pregnant women)

Causes sepsis in newborns

Generally treated with antibiotics during labor

GBS

Vaccines•Pure polysaccharide•Protein conjugate vaccines (phases I, II)

Challenges•Multiple serotypes

Link to the Jordan Report from NIP websiteLink to the Jordan Report from NIP website

Vaccine-preventable diseases and

adolescents: why so many cases?

Pertussis

Pertussis Impact Among Pertussis Impact Among Adolescents & AdultsAdolescents & Adults

Pneumonia (2%) Pneumonia (2%)

Rib fractures (1%)Rib fractures (1%)

Hospitalization (~1%)Hospitalization (~1%)

Medical costsMedical costs

Missed school and work Missed school and work

Impact on public health systemImpact on public health system

Loss of sleep; loss of consciousnessLoss of sleep; loss of consciousness

Weight lossWeight loss

Why Adolescents & Adults need Pertussis Vaccine

In 2003 pertussis In 2003 pertussis vaccinevaccine levels in children 19-35 levels in children 19-35 months highest evermonths highest ever

Pertussis Pertussis casescases continued to rise continued to rise

2005 – 25,616 pertussis cases, 2005 – 25,616 pertussis cases, highest recorded since 1959 highest recorded since 1959

– 67% of cases - adolescent or adult 67% of cases - adolescent or adult

– Overall incidence is 8.7/100,000Overall incidence is 8.7/100,000

– Infants < 6 months 160.8/100,000Infants < 6 months 160.8/100,000

Pertussis immunity wanes in 5-10 yearsPertussis immunity wanes in 5-10 years

Pertussis Trends in the U.S.

1994-2004 reported cases, 5x higher1994-2004 reported cases, 5x higher

2001-2005* - 109 pertussis-related deaths 2001-2005* - 109 pertussis-related deaths

88/109 or >80% who died were too young to 88/109 or >80% who died were too young to have completed a primary series of DTaPhave completed a primary series of DTaP

Source of infection most often an older child Source of infection most often an older child or adult in the householdor adult in the household

*2001-15; 2002-22; 2003-18; 2004-16; 2005-38 CDC unpublished *2001-15; 2002-22; 2003-18; 2004-16; 2005-38 CDC unpublished datadata*2001-15; 2002-22; 2003-18; 2004-16; 2005-38 CDC unpublished *2001-15; 2002-22; 2003-18; 2004-16; 2005-38 CDC unpublished datadata

Why Pertussis in Adolescents?

Waning immunityImproved diagnosticsImproved surveillance

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

Pertussis Vaccines - TdapPertussis 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

Adolescent-Adult Pertussis Vaccination Objectives

PrimaryPrimary– Protect vaccinated adolescentsProtect vaccinated adolescents

– Continue protection after completion of initial Continue protection after completion of initial seriesseries

SecondarySecondary– Reduce Reduce B. pertussisB. pertussis reservoir reservoir

– Reduce pertussis incidence in other age groupsReduce pertussis incidence in other age groups

General Principles Use of Tdap and Td

Tdap is preferred for protection against pertussis

Tdap is licensed for ONE single dose at this time

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

*if the person has completed the recommended childhood DTaP vaccination series, and has not yet received a Td booster

Persons >10 years with NOHistory 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

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

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 2nd or 3rd trimester is preferred

**See section 3-K in Adolescent Tdap ACIP RecommendationsSee section 3-K in Adolescent Tdap ACIP Recommendations

Schoeller T, Schmutzhard E. Schoeller T, Schmutzhard E. N Engl J Med. N Engl J Med. 2001;344:13722001;344:1372 Schoeller T, Schmutzhard E. Schoeller T, Schmutzhard E. N Engl J Med. N Engl J Med. 2001;344:13722001;344:1372

Meningococcal Disease

Rates of Meningococcal Disease* by Age, 11-30 y/o, United States, 1991-2002

0

0.5

1

1.5

2

2.5

11 13 15 17 19 21 23 25 27 29

Age (yr)

Rate

s pe

r 100

,000

ABCs NETSS

* Serogroups * Serogroups A/C/Y/W135* Serogroups * Serogroups A/C/Y/W135

U.S. RateU.S. Rate

Risk Factors for Meningococcal Disease in the United States

Deficiencies in the terminal complement pathway

Functional or anatomic aspleniaHIV infectionSmokingPassive exposure to smokeUpper respiratory tract infectionCrowding

18-23 years old 1.4 / 100,000

18-23 years oldnot college student 1.4 / 100,000

Freshmen 1.9 / 100,000

Freshmen in dorm 5.1 / 100,000

18-23 years old 1.4 / 100,000

18-23 years oldnot college student 1.4 / 100,000

Freshmen 1.9 / 100,000

Freshmen in dorm 5.1 / 100,000

Meningococcal Disease Among Young Adults, United

States, 1998-1999

Bruce et al, JAMA 2001;286;688-93Bruce et al, JAMA 2001;286;688-93

Approved by FDA Approved by FDA January 2005January 2005Approved by FDA Approved by FDA January 2005January 2005

MenactraTM

(sanofi pasteur)Quadrivalent (serogroups A, C, Y, W-135)

conjugated to diphtheria toxoidApproved for persons 11-55 years of ageSchedule: 1 doseAdministered by intramuscular injection

Meningococcal Conjugate Vaccine

Meningococcal Conjugate Vaccine

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

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) MMWR 2005;54(RR-7)

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

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*except to avoid vaccination of persons with a history of GBS who are not at increased risk of infection

Newsweek: 1 May 2006 Dubuque, Iowa

1956 Philadelphia

Why Mumps in Adolescents?

Highly communicableImperfect vaccine efficacy

• 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

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

Adolescent Vaccination

Questions?