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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?