Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Designing vaccines for specific populations and germs - Slides by Professor Esposito

38 views

Published on

The presentation given by Professor Susanna Esposito at ECCMID 2019. A view on vaccines recommendations, combined vaccinations and impact of vaccination practices in the eradication of major infectious diseases.

To learn more, please visit www.waidid.org

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

Designing vaccines for specific populations and germs - Slides by Professor Esposito

  1. 1. DESIGNING VACCINES FOR SPECIFIC POPULATIONS AND GERMS Susanna Esposito Pietro Barilla Children’s Hospital University of Parma, Parma, Italy
  2. 2. Disclosures Research Grants: Abbott, DMG, GSK, Janssen, Sanofi-Pasteur, Vifor Advisory Board Membership: GSK, Janssen, MSD, Sanofi-Pasteur, Pfizer, Vifor
  3. 3. 3 How many lives are saved by vaccines? 2.5 million per year 7,000 per day 300 per hour 5 per minute WHO – 2011-2020
  4. 4. DDF 4 THE RISE OF LIFE EXPECTANCY
  5. 5. Facultad de Medicina Universidad de Chile Berkeley, 17 maggio 1749 – Berkeley, 26 gennaio 1823
  6. 6. Smallpox Eradication Timeline Year Milestone 1959 WHA adopts goal to eradicate smallpox -reliance on compulsory vaccination and revaccination of 80% of the population through campaigns using freeze-dried vaccine 1966 Inadequate supplies in a West African outbreak facilitated use of the surveillance/containment approach, after scale up in other countries in the region smallpox disappears in 3.5 years 1967 Global Smallpox Eradication Program officially launched by WHO -44 countries (31 had endemic smallpox) reported 217,218 cases 1968 WHO Scientific Group promotes both mass vaccination and surveillance/containment as “co-strategies”. India adopts surveillance/containment. 1974 Bihar, India identifies 1500 new cases of smallpox every day 1977 Last case of naturally-acquired smallpox occurred in Merca District of Somalia 1980 WH0 certified the world free of naturally-occurring smallpox, routine vaccination ceased
  7. 7. Over 200 years of Vaccine Development!!
  8. 8. Perugia 2017
  9. 9. Poliovirus Vaccine • 1955 Inactivated vaccine • 1961 Types 1 and 2 monovalent OPV • 1962 Type 3 monovalent OPV • 1963 Trivalent OPV • 1987 Enhanced IPV (IPV)
  10. 10. Polio Vaccination Recommendations • Sequential schedule with 2 IPV and 2 OPV in 1999-2001 • Exclusive use of IPV recommended in 2002 • VAPP eliminated
  11. 11. … at least 19 recommended UMV! Rationale of combined vaccines in infants and toddlers - Knuf 13
  12. 12. A: universal recommendation; B: recommendation for specific cohorts; N: catch-up Europäisches Zentrum für Krankheitskontrolle und Prävention (ECDC). Vaccine schedule. http://vaccine-schedule.ecdc.europa.eu/Pages/Scheduler.aspx (Abgerufen im April 2017) Vaccination calendar for infants and toddlers in five european countries France Germany Italy Spain UK France Germany Italy Spain UK F D I E UK France Germany Italy Spain UK France Germany Italy Spain UK France Germany Italy Spain UK PertussisHib Hepatitis B Diphtherae Polio- myelitisTetanus B B B A B A A A A A A A A A A A A A N N A A A A A A A A A A A A A A A A A N A A A A A A A A A A A A A A A A N A A A A A A A A A A A A A A A A A A A A A A A A N N N A A A A A A A A A A A A A A A A A A A A A A A A up to 3 years up to 3 years up to 16 yeras up to 18 years up to 3 years up to 7 years up to 3 years birth Rationale of combined vaccines in infants and toddlers - Knuf 14
  13. 13. Perception of ‘too many’ shots may affect vaccine coverage • Vacc schedules require more than one shot in each visit1 – Parents anxiety may drive them to postpone or avoid some vaccines2 • Vaccine delay: – Driver to receive less vaccines, especially in small infants3 – Increase infections and diseases2,3 ✘ 1. Centers for Disease Control and Prevention (CDC). Recommended immunization schedule for children and adolescents aged 18 years or younger, 2. United States, 2017. https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf Accessed May 21, 2017. 3. Bielicki JA, et al. Vaccine. 2013;31(46):5375–5380. 4. Luman ET, et al. JAMA. 2005;293(10):1204–1211.
  14. 14. Combined vaccines: History • Multi antigen – 1945: Influenza (3 antigens)1,2 – 1947: S. pneumoniae (6 antigens)1,2 – 1955: IPV (3 antigens)1,2 • Multi valent – 1948: DTPw1,2 – 1960: DTPw IPV1,2 – 1971: MMR1 – 1990: DTPw Hib2 DTPw IPV Hib2 1. Decker. PIDJ 2001;20(Suppl.1):S10–8 2. Decker y cols. 2004. In: Vaccines Ch 29
  15. 15. Why combinations? • Less pain • Simplicity of administration • Simplicity of program • Improved compliance • Improved effectiveness • Lower costs Rationale of combined vaccines in infants and toddlers - Knuf 17
  16. 16. Potentially interactions between vaccine components Possible adverse consequences: • reduced immunogenicity • increased reactogenicity • shortened shelf life • complicated manufacture Antigens Preservative(s) Adjuvant(s) Contaminants pH Stabiliser(s) Excipient(s) Rationale of combined vaccines in infants and toddlers - Knuf 18
  17. 17. Hexavalent vaccines Vaccine Producer Year of Licensure • (DTaP2-IPV-HepB/Hib) SP-MSD 2000-2005 • DTaP3-IPV-HepB/Hib GSK 2000 • DTaP2-IPV-HepB-Hib SP 2013 • DTaP5-IPV-HepB-Hib MCM (MSD/SP) 2016
  18. 18. Reduction of Hib-associated diseases in Europe due to vaccination programs Eskola J. Foresight in medicine: current challenges with Haemophilus influenzae type b conjugate vaccines. J Intern Med. 2010;267(3):241-250 UK Finland The Netherlands Ireland Israel -1 0 1 2 3 4 5 6 0 20 40 60 80 100 120 Years after introduction of a Hib-combined vaccine Hib-incidence(in%)afterimplementationof vaccinationcorrespondingtoinciidencebevor introductionofHib-vacconation(%) Annual incidence of Hib-associated infectious diseases after introduction of a Hib-vaccination program
  19. 19. Impatto della varicella in Europa/anno Impatto della varicella in Europa/anno/età
  20. 20. Varicella incidence rates based on mandatory notifications (x 1.000) and hospitalization rates (x100.000) due to varicella in 8 Italian Regions (2003-2012) • Annual incidence rate 0.8 (2003)  0.2 (2012) • Hospitalization rate 3.3 (2005) 1.1 (2012) • Annual incidence rate 1.1 (2003)  0.6 (2012) • Annual incidence rate 1.0 (2003)  0.1 (2012) • Hospitalization rate 3.4 (2003)  0.5 (2012) • Annual incidence rate 3.2 (2004)  0.4 (2012) • Hospitalization rate 5.3 (2004)  1.2 (2012) • Annual incidence rate 3.9 (2003)  3.7 (2012) • Hospitalization rate 2.3 (2003)  2.1 (2012)• Annual incidence rate 3.0 (2003)  0.4 (2012) • Hospitalization rate 3.2 (2003)  0.8 (2012) • Annual incidence rate 1.4 (2003)  0.3 (2012) • Hospitalization rate 1.8 (2003)  0.5 (2012) • Hospitalization rate 3.8 (2003)  1.8 (2012) • Annual incidence rate 1.1 (2003)  0.1 (2009) • Hospitalization rate 4.8 (2003)  0.8 (2012)
  21. 21. Fever Seizures
  22. 22. Czajka H et al, Vaccine 2009 …… measles antibody titer after receipt of MMRV was associated positively with the rate of fever. Use of separate MMR and varicella vaccines averts the slight increase in risk of fever and febrile seizures after MMRV administration……..
  23. 23. MMRV 1
  24. 24. Pertussis: Age-related incidence (USA) Rationale of combined vaccines in infants and toddlers - Knuf 28
  25. 25. Complications of Pertussis in Children  4 Years of Age in the US, 1997‒2000 Age Hospitalization Pneumonia Seizures Encephalopathy Death No. with Pertussis < 6 M 4,543 847 103 15 56 7,203 6‒11 M 301 92 7 1 1 1,073 1‒4 Y 324 168 36 3 1 3,137 CDC. MMWR 2002;51(4):73‒76
  26. 26. 30Infect Immun 2001
  27. 27. Pertussis prevention strategies throughout life 0 3 months Adolescents AdultsChildren Waning immunity1 Vaccine induced protection1 Limited natural immunity1 Transmission2,3 Elderly 1. Adapted from Wendelboe et al. Pediatr Infect Dis J 2005: 24; S58–S61; 2. Sawyer, Chair ACIP Pertussis Vaccine WG, Oct 24, 2012; 3. CDC. MMWR 2011; 60: 13–15; 4. Tan & Gerbie, Obstetrics Gynecol 2013; 122: 370–3; 5. CDC. MMWR 2011; 60: 1117–23; 6. CDC. MMWR 2012; 61; 66–72; 7. CDC. MMWR 2013; 62: 66–72; 8. Healy et al. Clin Infect Dis 2011; 52: 157–62
  28. 28. Department of Health Sciences University of Florence all adolescents and adults receive the Tdap vaccine to replace the scheduled tetanus and diphtheria toxoids vaccine (Td) booster all people who have or anticipate having close contact with infants <12 months of age receive a single dose of Tdap, all immediately postpartum women who have not previously received a Tdap vaccine receive a dose prior to leaving the hospital. Recommendations have now been expanded to routinely immunize all adults 65 years of age and older with a single dose of Tdap; administer a booster dose of Tdap with each pregnancy, regardless of interval between pregnancies, ideally after the 20th week of gestation.
  29. 29. Countries with cocooning recommendations 1. Australian Immunisation Handbook 9th edition 2008; Part 2.3.2, available from: http://www.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook- specialgroups (accessed June 2011); 2. Kinkhoest (pertussis) – vaccinatie. Available from: http://www.zorg-en-gezondheid.be/Ziektes/Vaccinaties/Vaccins-A-Z/Kinkhoest- %28pertussis%29---vaccinatie/ (accessed June 2011; 3. Haut conseil de la santé publique. Bulletin Épidémiologique Hebdomadaire 2009;16–17:46–76; 4. Impfempfehlungen der Ständigen Impfkommission am Robert Koch-Institut/Stand: Juli 2010. Epidem Bull 2010;30:279–98; 5. New Zealand Ministry of Health Immunisation Handbook 2011; Ch 6; 6. CDC. MMWR 2011;60:13–5; 7. http://www.cdc.gov/vaccines/recs/provisional/default.htm (accessed August 2011); 8. WHO vaccination schedule, available from: http://apps.who.int/immunization_monitoring/en/globalsummary /ScheduleSelect.cfm (accessed June 2011) Country with cocooning recommendatio n Country without cocooning recommendation
  30. 30. Department of Health Sciences University of Florence Hasala,2008  the results of neonatal vaccination with DTaP vaccine in 50 infants between 2 to 14 days of age. The administration of an additional dose at birth was safe and well tolerated, but was associated with lower geometric mean antibody concentration for toxin and pertactin fimbrae, diphtheria efficacia del vaccino della vaccinati alla nascita [n: 45] età anti-PT anti-FHA anti-PRN 3 mesi 8.7 4.3 13.0 5 mesi 41.2 29.4 70.6 6 mesi 60.9 39.5 82.6 12 mesi 87.5 42.5 85.0 Belloni C et al. Pediatrics 2003; 111: 1042-1045 pertosse somministrato alla nascita Vaccination in the neonates
  31. 31. Lancet 2014
  32. 32. VACCINE EFFECTIVENESS ACCORDING TO TRIMESTER OF PREGNANCY (Winter et al., Clin Infect Dis 2017)
  33. 33. Immune Responses and Antibody Decay after Immunization of Postpartum Women with Tetanus and diphtheria toxoids and acellular pertussis vaccines (Tdap) Fortner KB1, Hunter DL2, McDonald WL2, Rock MT2, Edwards KM2 1Division Maternal-Fetal Medicine, Vanderbilt University 2Division Pediatric Infectious Disease, Vanderbilt University Are Tdap Vaccines Needed with Each Pregnancy?
  34. 34. Department of Health Sciences University of Florence total of 21 studies were included in this review. OR 0.47 to 1.50 for preterm birth (less than 37 weeks of gestation) 0.65-1.00 for small for gestational age (birth weight less than the 10th percentile) 0.36-0.85 for stillbirth 0.16-1.00 for neonatal death 0.76-1.20 for low birth weight (less than 2,500 g) 0.20-0.91 for congenital anomalies All lower 95% confidence intervals (CIs) were less than 1.0. Of three retrospective studies assessing chorioamnionitis after vaccination, one showed a small but statistically significant increase. Safety of Tetanus, Diphtheria, and Pertussis Vaccination During Pregnancy: A Systematic Review. McMillan M. Obstetrics & Gynecology 2017; 129:560-73
  35. 35. The risk groups by age of seasonal influenza ESPID 2013 *Based on 3930 US cases from 2007-2008. Soucres: WHO, CDC; American Journal of Hygiene
  36. 36. Effect of Age on Healthcare Burden <6 months 6–12 months 1–<3 years 3 –<5 years 5 –<15 years Excesseventsper100children Outpatient visits16 14 12 10 8 6 4 2 0 Courses of antibiotics Excess treatment events in otherwise healthy children under 15 years of age; data over 19 consecutive seasons (US) Neuzil KM, et al. N Engl J Med 2000;342:225–31. Age
  37. 37. Subjects(%) 0 5 10 15 20 25 30 35 40 45 Acute otitis media Pneumonia Sinusitis Antibiotics <3 years 3–6 years 7–13 years Complications of influenza in different age groups, prospective cohort study, Turku, Finland, 2000–2002 Children Under 3 Years of Age are Most Likely to Develop Acute Otitis Media and Require Antibiotics Heikkinen T, et al. J Infect Dis 2004;190:1369–73.
  38. 38. Mortalityrate per1,000people 0 0.02 0.04 0.06 0.08 0.10 6–23 months 2–4 years 5–9 years 10–19 years 20–49 years 50–64 years ≥ 65 years < 6 months Age group Age-associated rates of influenza-related deaths; data from British Columbia, Canada, 1998–2004 influenza seasons Mortality Rates due to Influenza and Pneumonia Sebastian R, et al. Vaccine 2008;26:1397–1403. Provincial and national influenza surveillance reports from the British Columbia Centre for Disease Control, the Public Health Agency of Canada’s FluWatch Program, and the Canada Communicable Disease Report (CCDR) were analysed from 1 Sep 1998 to 31 Aug 2004, to determine influenza-related deaths in British Columbia, Canada.
  39. 39. Season 2007/2008 Seasonal A/H1N1 (n=126) Season 2008/2009 Seasonal A/H3N2 (n=486) Season 2009/2010 Pandemic A/H1N1 (n=389) CLINICAL OUTCOME Hospitalisation rate, n (%) Duration of hospitalisation, mean days ± SD Absence from school, mean days ± SD 4 (3.1)°* 5.1 ± 3.5°* 5.9 ± 4.7°* 79 (16.3) 7.5 ± 4.4* 7.5 ± 3.4* 51 (13.1) 9.1 ± 7.5 8.9 ± 5.3 DRUG USE, n (%) Antibiotics Antivirals Antipyretics Aerosol therapy Steroids 99 (78.6)° 0 (0.0)* 100 (79.4)°* 30 (23.8)°* 6 (4.8) 466 (95.9) 0 (0.0)* 460 (94.6) 203 (41.8) 36 (7.4) 297 (76.3)° 16 (4.1) 383 (98.5) 157 (40.4) 23 (5.9) °p<0.01 vs seasonal A/H3N2 influenza; *p<0.01 vs pandemic A/H1N1 influenza Clinical Outcomes and Drug Use by Influenza A Subtypes Esposito S, et al. J Infect 2011;63:300−7.
  40. 40. 0 20 40 60 80 100 Clinical presentation in children with influenza A and B infection is similar Esposito S, et al. BMC Infect Dis 2011; 11: 271. LRTI, lower respiratory tract infection. Influenza A/H1N1 (n = 143) Influenza A/H3N2 (n = 519) Influenza B (n = 239) Children with influenza A/H3N2 had an higher number of LRTI, wheezing and pneumonia than those with influenza A/H1N1 o B (all p < 0.05) Percentage
  41. 41. Influenza vaccination recommendations WHO/Europe Recommend that member states vaccinate all individuals ≥6 months1 EU Member states currently recommend paediatric vaccination;2,3,4 recommendations vary by country: • 6 months to <18 years of age: Austria, Estonia and Slovakia • 6–35 months: Finland • 6–24 months: Slovenia, Latvia • 24 months-10 yrs: UK USA, Canada and PAHO countries • US: All individuals ≥6 months of age5 • Canada: Children 6–24 months of age, and encourages all individuals ≥6 months of age to be vaccinated6 • Currently, 27 PAHO countries and territories recommend paediatric seasonal influenza vaccination7*
  42. 42. Age group and costs (€) Without vaccination With vaccination Total savings 6 months to <3 years (N=140 000) Medical costs 3 473 091 694 521 2 778 571 Vaccination program costs 0 1 057 916 -1 057 916 Health care costs 3 473 091 1 752 437 1 720 654 Travel costs 247 972 889 016 -641 043 Total direct costs 3 721 064 2 641 453 1 079 611 Productivity costs 3 355 692 1 631 008 1 724 684 Societal costs 7 076 756 4 272 461 2 804 295 Assumed vaccine efficacy 60%. Vaccination of young children is cost-saving, investing €1 million will save an estimated €2.8 million in societal costs Influenza vaccination in young children is cost effective Salo et al. Vaccine 2006 The Finnish experience (assumed vaccine efficacy 60%)
  43. 43. MICROBIOTA and EPIGENETIC PROGRAMMING Heredity deals the cards; environment plays them
  44. 44. Messieurs, c'est les microbes qui auront le dernier mot. Louis Pasteur 1822-1895
  45. 45. I AM VACCINATED. WHAT ABOUT YOU?

×