A Review of Pediatric Vaccines Gary Overturf, M.D. Professor of Pediatrics, Inf. Dis. University of New Mexico

Transcription

1 Review of Pediatric and Adolescent Vaccines 2012 Idaho Society of Health- System Pharmacists Boise, ID April 28 th 2012

2 A Review of Pediatric Vaccines Gary Overturf, M.D. Professor of Pediatrics, Inf. Dis. University of New Mexico

3 Conflicts of Interest for: Dr. Gary Overturf Member and Chair, Advisory Board for Merck Vaccines and speaker for Merck Vaccines; 2006 to the present Speaker and Advisory Board for SanofiPasteur Vaccines; 2006 to the present Speaker and or Consultant for MedImmune and Novartis Vaccines; present Member and Past Chair of FDA Vaccine and Related Biologics Advisory Committee ( ). Liaison member from American Academy of Pediarics to the CDC ACIP Member of the American Academy of Pediatrics Infectious Diseases (RED BOOK) Committee, ; Associate Editor, RED BOOK 2003.

4 Routinely Recommended Vaccines for Children & Adolescents Children Diphtheria, Tetanus, Pertussis (DTaP Polio (IPV) Hepatitis B (HBV), Hepatitis A (HAV) Haemophilus (type b) conjugate vaccine (Hib) Pneumococcal conjugate vaccine (PCV) Rotavirus vaccine Measles/Mumps/Rubella (MMR, MMRV) Varicella Adolescents Diphtheria, tetanus, pertussis booster (Tdap) Human papillomavirus vaccine (HPV) Meningococcal conjugate vaccine (MCV4)

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8 Antigenic Components of Bordatella pertussis FIM FHA PT Filamentous hemagglutinin (FHA) Pertussis toxin (PT), also known as lymphocytosis-promoting factor (systemic action) Pertactin (PRN) or 69 kd* protein PRN Fimbrial agglutinogens (FIM) (1-4 serotypes) *kd = kilodalton. Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;

9 Tdap: Boostrix vs. Adacel and the infant correllates: Infanrix vs. Daptacel Component Tetanus Toxoid Dipth. Toxoid Pertussis Toxoid FHA Pertactin Boostrix Infanrix Daptacel Adacel 5.0 Lf 10.0 vs Lf 2.5 Lf 25.0 vs Lf 8.0 ug 25.0 vs ug 8.0 ug 25.0 vs ug 2.5 ug 8.0 vs ug Fimbria 2/3 0 0 vs ug Adjuvant Preservative AlOH 3 None NO Thimerosol AlOH 3 0.6% POE

10 Antibody Type vs. Efficacy FIM Pattern of Antibodies* PRN PT Protective Efficacy (95% CI) High High High or Low 85% (65 94%) High Low High or Low 72% (22 90%) Low High High or Low 75% (0 96%) Low Low High or Low 46% (14 66%) * High (>5 units) or Low (0 to <5 units) levels of antibody before pertussis exposure. Efficacy against WHO-defined pertussis. (Storsaeter et al, Vaccine 1998;16: )

11 T-Cell Independent Immune Response (Polysaccharide Vaccines) IgM Ab IgG Ab Total Ab Ab Titer 1 o Ag 2 o Ag Time After Immunization

12 T-Cell Dependent Immune Response (Conjugate Vaccines) IgM Ab IgG Ab Total Ab Ab Titer 1 o Ag 2 o Ag Time After Immunization

13 Incidence of Invasive Hib Disease in Children <5 Years of Age, Canada, ,000 Rate per Pentacel Vaccine Introduced Year Data for are provisional. Reference: 1. Public Health Agency of Canada, CCDR. 2006;32S3:15.

14 Haemophilus influenza type b Available Vaccines, U.S. H. influenzae, type b: : pleomorphic gram negative rod, one of 6 types with distinct capsular polysaccharide; before immunization was the most common cause of meningitis and epiglottis in children 6 18 mo, 2 4 yr, respectively. Licensed/recommended for use in U.S. 1989; 3 or 4 doses depending on vaccine conjugate type Conjugate preparations (U.S.): ActiHib (PRP-T), 2, 4, 6 and months PedvaxHib (PRP-OMP); 2, 4, months HibTITER (PRP-CRM 197 ) Combinations: Comvax, Pentacel, Pediarix

15 Pneumococcal Vaccines in U.S. Streptococcus pneumoniae, gram positive diplococcus, 90 types of capsular polysaccharide; often resistant to betalactamase antibiotics (modification pcn-binding proteins); invasive pneumococcal disease most prevalent in children < 2 yrs and adults > 65 yrs and high risk populations (e.g. SCD) Polysaccharide vaccines (PPS23) is expected to have a diminishing role in U.S. immunization policy Only one vaccine conjugates in U.S. licensed pneumococcal vaccines (CRM 197 ), Prevnar PCV7 (4,6B,9V,14,18C,19F,23F) PCV13 (the above+1,3,5,6a,7f,19a) 4-dose series: 2,4,6 and mos; additional regimens for high risk children up to age 59 mos.

16 Inactivated Polio Vaccines (IPV) Polio eliminated in the Western Hemisphere since 1996, except for OPV related cases, thus IPV no longer recommended, licensed or available in the U.S. Polio cases still occur in India, Pakistan, Afghanistan and central Africa. IPV preparations in U.S. include: trivalent inactivated and combination products. Trivalent inactivated vaccines (IPV) are given in four doses at 2,4,6-18 mos with 4 th dose after 4 yrs (4-6yr).

17 Hepatits B Immunization Immunoprophylaxis of Newborn infants born to HBsAg+ mothers: Hepatitis B vaccine + HBIG within 12 hours of birth; followup varies with infants < 2000 vs > 2000 grm birth weights. Routine childhood immunization with either Recombivax or Energix-B ; 5µg and 10µg protein per 0.5 ml, respectively. Many variants schedules recommended for high-risk or normal adolescents. Basic 3-dose Schedule: AAP stongly endorses the newborn-1 st dose at birth six weeks which must be a single antigen. 1 st dose: birth six weeks 2 nd dose: 2 mos 3 rd dose: 4 mos 4 th dose: given after 6 mos NOTE: a 4 th dose may be given if a birth dose was used, but 3 dose series is the basic series.

18 Hepatitis A Immunization Initial states included: CA, AZ, NM, TX and OK. There has been a marked decline in all states since licensure of the vaccine in 1995; e.g. 22,000-36,000 case/yr , 1995, with only 2975 cases in HAV available in the U.S. include: Havarix, Vaqta as well as Twinrix (HAV+HBV, licensed only for persons 18 yr or older) Recommendation is for first dose at > 12 mos, second dose for 6-12 mos later.

19 Available Combination Vaccines Available for many years: : DTP & DTaP, MMR & MMRV, HepB/Hib and multivalent vaccines (IPV, OPV, meninogococcal & pneumococcal vaccines, and trivalent influenza vaccines. Pediarix (GSK): DTaP/HepB/IPV, for use at 2, 4 and 6 months (note: no booster approval). Hib/DTaP/IPV Pentacel (SanofiPasteur): DTaP/Hib/IPV, for use at 2,4,6 & months of age, reducing 3 injections to one. DTaP/IPV (Kinrix TM ; GSK), reducing to 2 injections needed at 4 6 yrs of age (e.g. with MMRV)

20 Pentacel Vaccine Description 1 Indication: Active immunization against disease caused by Diphtheria Tetanus Pertussis Poliomyelitis types 1-3 Haemophilus influenzae type b (Hib) Dosing: 4-dose series Infant: 2, 4, and 6 months of age Toddler: months of age Reference: 1. Pentacel vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc.; 2008.

21 Simplifying the Infant-Toddler Immunization Schedule With Pentacel Vaccine (DTaP-IPV/Hib) 1 Vaccine Age Birth 1 month Range of recommended ages 2 months 4 months 6 months 12 months 15 months 18 months Hepatitis B Rotavirus HepB HepB Rota Rota Rota HepB Diphtheria, Tetanus, Pertussis Haemophilus influenzae type b Pentacel Vaccine Pentacel Vaccine 4 Inactivated Poliovirus PCV Influenza (Yearly) Pneumococcal PCV PCV PCV MMR Influenza Varicella Measles, Mumps, Rubella HepA (2 doses) Varicella Hepatitis A

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23 Rotarix (Rotavirus Vaccine, Live, Oral) 1 Human Rotavirus G1P1A[8] Attenuated by serial passage in cell culture Rotarix G1P1A[8] 1. Rotarix Prescribing Information. Accessed July Rotarix (Rotavirus Vaccine, Live, Oral) is a registered trademark of GlaxoSmithKline.

24 RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) 1 Bovine (WC3) Rotavirus P7[5] (VP4) G6 (VP7) G1P1A[8] Human Rotavirus G2P2[6] Human G3P1A[8] Human G4P2[6] Human Rotavirus Rotavirus Rotavirus G1 (P7[5]) P1A[8] (G6) G2 (P7[5]) G3 (P7[5]) G4 (P7[5]) Human Bovine Reassortant Rotavirus Vaccine Strains 1. Offit PA, Clark HF. Pediatr Ann. 2006;35:29 34.

25 Rotavirus Structure 1 Inner Capsid (VP6, subgroup antigen) Core Capsid (VP2) Segmented dsrna genome VP7 (G serotype) VP4 (P serotype) Outer capsid Triple-layered layered viral capsid surrounds 11 segments of ds RNA VP7 and VP4 induce neutralizing antibodies VP7 determines G serotypes; VP4 determines P serotypes VP6 is the target antigen for diagnosis of rotavirus disease 1. Adapted from Parashar UD et al. EID 1998;4:

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28 Adolescent Vaccines Tdap HPV MCV4

29 HPV Vaccines Gardasil TM (Merck Inc): Oncogenic types 16, 18 & papilloma (wart) types 6, 11 Cervarix (GSK): Oncogenic types 16, 18 with enhanced adjuvants.

30 Gardasil Quadrivalent HPV Vaccine Antigens: HPV 16 and 18 (70% of associated HPV cervical carcinoma), plus HPV 6 and 11 (genital warts); recombinant vaccine w/o live viruses. FDA VRBPAC approved GARDASIL on May 18, 2006 and it was licensed June 6 th. CDC ACIP recommendations, June 29th 2006 Licensure based largely on a demonstrated efficacy of of virtually 100% in preventing new infections and progression to cervical dysplasia (e.g. CIN 2/3 and AIS cervical lesions) in women.

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35 ACIP Recommendations for HPV4 for Males (October 25, 2011) MMWR, Dec 23, HPV4 efficacy for males against HPV 6 & 11, 16 & 18 genital lesions (warts) was 88.1%. In 3 trials, HPV4 had an efficacy of 77.5% against AIN 1, 2, 3 among males and females. No studies have evaluated the efficacy of HPV4 for prevention of recurrent papillomatosis or oropharyngeal cancers Recommendations for HPV4 (Gardasil) for males: ACIP recommends routine vaccination of males age 11 or 12 years with HPV4 as a 3-dose series. The vaccination can be started at age 9 years. Vaccination with HPV4 is recommended for males aged years who have not completed the 3-dose series. Males may be vaccinated.

36 Meningococcal Vaccines Available Vaccines*: Monovalent & Multivalent Polysaccharide Vaccines Menomune (SanofiPasteur) Meningococcal C conjugate vaccine (UK). Menactra (SanofiPasteur). Menveo (Novartis) *Current U.S. licensed vaccines in bold type.

37 Impact of Polysaccharide Meningococcal Vaccines in the US Military 500 Monovalent (group C) 35 Hospitalizatio ons (n) Bivalent (A/C) Quadrivalent (A/C/Y/W-135) Incidence e Rate (per 100,000 per rson - years) *Bars indicate hospitalization frequencies; line indicates rates DeFraites RF. MSMR. 2000;6:2. Year 0

38 Summary: Rationale for MCV4 in Adolescents Adolescents have the 2 nd highest attack rate for meningococcal disease & high carrier rates. Adolescents have the highest mortality rates with meningococcal infection Adolescents have infections with serotypes that can be prevented by the available vaccines Conjugate vaccines provide memory responses and eliminate carriage which leads to a herd effect

39 Menactra versus Menveo Menactra : PS-phenol inactivated diphtheria toxin conjugate; Menveo is a CRM-197 conjugate (spontaneous non- toxic diptheria toxin). Head to head trials have shown Menveo produces statistically significant higher rates of presumed protective antibodies for serotypes A, W135 & Y, at 1 and 24 mos, but, antibody decline is equivalent to Menactra ; clinical significance is unknown, levels at months of age are not significantly different. Currently Menveo is licensed for adolescents and adults (11-55 yrs) and high risk children (2 10 yrs). Currently, Menveo is approved for use in adolescents similar to Menactra including the need for a 2 nd dose 5 years after the first dose. The FDA and the ACIP have stated no preference for either vaccine

40 ACIP Recommendations for: Meningococcal Conjugate Vaccines Routine, for all adolescents at the year old visit & all adolescents who have not been vaccinated. (children should be 1 st immunized at 11 and given a 2 nd dose at yrs) ACIP (9/25/2009) recommends that persons immunized > 7 yrs & at prolonged increased risk should be re- vaccinated at 5 yrs.. including entering college students who plan to live in dorms (other shared multi-housing). Persons at increased risk: terminal complement deficiency, properidin or factor H or D deficiency; asplenia (if immunized at 2 6 yrs, should be re- vaccinated at 3 years). Microbiology technologists; Travelers to hyperendemic areas; Others who may wish to control their risk; and control of disease outbreaks

41 Supplemental ACIP Recommendations for Meningococcal Conjugate Vaccines ACIP Working group recommendations from the October 27, 2010 ACIP Meeting (MMWR, January 28, 2011) Routine vaccination of adolescents at yrs with a booster dose at 16 yrs. A 2 dose primary series administered 2 months apart for persons aged 2 54 yrs with complement component deficiency (C5-C9, C9, properidin, factor H or D), functional/anatomic asplenia, and adolescents with HIV infection.