1 / 48

Meningococcal Vaccines The Journey Continues

Meningococcal Vaccines The Journey Continues. Canadian Public Health Association Conference June 19, 2011. Bryna Warshawsky, Associate Medical Officer of Health 519-663-5317 ext. 2427; bryna.warshawsky@mlhu.on.ca. Outline. Background Epidemiology Journey Polysaccharide vaccines

mulan
Télécharger la présentation

Meningococcal Vaccines The Journey Continues

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Meningococcal VaccinesThe Journey Continues Canadian Public Health Association Conference June 19, 2011 Bryna Warshawsky, Associate Medical Officer of Health 519-663-5317 ext. 2427; bryna.warshawsky@mlhu.on.ca

  2. Outline • Background • Epidemiology • Journey • Polysaccharide vaccines • Conjugate C vaccines • Conjugate quadrivalent vaccines • Meningococcal A vaccine • Meningococcal B vaccines

  3. Background

  4. Meningococcal Disease • Neisseria meningitidis • Gram negative diplococci • Thirteen different serogroups, classified by their polysaccharide (sugar) capsule • Most common A, B, C, Y, W135 and X

  5. Meningococcal Disease • Causes: • meningitis - inflammation of the lining brain • meningococcemia - in the blood • Disseminated intravascular coagulation (DIC) • Presents as fever, headache, vomiting, stiff neck, photophobia and petechial rash • Fatal in approximately 10% • Long term sequelae 10 - 20% such as hearing loss, amputation or neurologic

  6. Immunogenicity • Vaccines authorized based on immunogenicity, not efficacy • Correlate of protection • Serum bactericidal antibody (SBA) titre • Dilution of serum able to kill meningococcal bacteria in vitro; requires the addition of complement • Using human complement correlate is ≥1:4 • Measure: • Percent achieving titre • Geometric mean titre

  7. Protection • Circulating antibody titre • Immune memory • May be too slow for post-exposure protection • Herd immunity

  8. Epidemiology

  9. Meningococcal by Year and SerogroupSource: NACI Statement, August 2009

  10. Meningococcal Epidemiology • 2006: • 210 cases in Canada • Serogroup C 43 cases 0.13/100,000 • Serogroup B 113 cases 0.34/100,000 • Serogroup Y 27 cases 0.08/100,000 • Serogroup W135 6 cases 0.02/100,000 • Serogroup A 2 cases 0.01/100,000 • Other 19 cases NACI Statement, CCDR, Volume 35 • ACS-3 April 2009

  11. The Journey

  12. Meningococcal A Quadrivalent conjugate A, C, Y and W135 Meningococcal B Conjugate C Polysaccharide A, C A, C, Y, W135 2001 1960 - 1980 2006 2010

  13. Polysaccharide Vaccines

  14. NACI Recommendation – Polysaccharide Vaccine • asplenic patients, sickle cell disease • complement deficient, properdin or factor D deficiency • travellers e.g. Hajj, Mecca, Saudi Arabia • laboratory workers who handle meningococcal specimens • military • close contacts of serogroups A, C, Y, W135 • outbreaks of serogroups A, C, Y, W135

  15. Conjugate C Vaccines

  16. Conjugate Vaccines • Sugar linked to a protein • diphtheria toxoid • diphtheria toxoid mutant – CRM 197 • tetanus toxoid • T cell dependent • Works in young children • Decreases carriage leading to herd immunity • Boostable response

  17. NACI RecommendationsMeningococcal C conjugate • Routine program: • 2 months to 4 year olds • adolescents • young adults • consider for 5-10 year olds • Post exposure for serogroup C • Outbreaks serogroup C NACI; CCDR, 2001; 27:2-36

  18. Richmond P et al. The Journal of Infectious Disease; 2001; 183:160-3

  19. Richmond P et al. The Journal of Infectious Disease; 2001; 183:160-3

  20. Quadrivalent ConjugateA, C, Y, W135

  21. Conjugate A, C, Y, W135 • MenactraTM (sanofi pasteur) – diphtheria toxoid • Authorized for use May 2006 • Authorized for ages 2 – 55 years • Not very immunogenic in infants • MenveoTM (Novartis ) - mutant diphtheria toxoid CRM197 • Authorized for use May 2010 • Mix lyophilized A with liquid C, Y, W135 • Authorized for ages 11-55 years • Has been shown to be immunogenic in infants

  22. NACI Recommendation • asplenic patients, sickle cell disease • complement deficient, properdin or factor D deficiency • travellers e.g. Hajj, Mecca, Saudi Arabia • laboratory workers who handle meningococcal specimens • military • close contacts of serogroups A, Y, W135 • outbreaks of serogroups A, Y, W135 • primary antibody deficiencies • HIV positive - consider

  23. NACI RecommendationAdolescent Vaccination • Meningococcal C conjugate or quadrivalent conjugate vaccines can be used depending on epidemiology and other considerations • Give an adolescent doses even if vaccinated at young age NACI, CCDR, May 2007;33(ACS-3):1-23 NACI, CCDR, April 2009;36(ACS-3):1-40.

  24. Jackson LA et al. Clinical Infectious Diseases 2009;49:e1-10 C non-inferior; others Menveo superior

  25. All Menveo superior Jackson LA et al. Clinical Infectious Diseases 2009;49:e1-10

  26. Effectiveness Data from US MenactraTM • 14 vaccine failures in the US • 8 serogroup C; 6 serogroup Y • Median age at vaccination 18 years (12-20 years) • Mean time from vaccination to disease 395 days (43-1021 day) • 3 underlying conditions • 3 fatal (21% case fatality) • Vaccine effectiveness estimated at 80-85% within 2 – 3 years after vaccination MacNeil et al. Pediatric Infectious Disease Journal, June 2011;30(6):451-455

  27. Effectiveness Data from US MenactraTM • Case control study – 108 cases; 158 controls • 78% effectiveness over 5 years of vaccination (95% CI: 29-93%) • Vaccinated < 1 year ago 95% (95% CI:10-100%) • Vaccinated 1 year ago 91% (95% CI:10-101% ??) • Vaccinated 2-5 years ago 58% (95% CI: -72% - 89%) • Waning protection over time ACIP; MMWR; January 8, 2011;60(3):72-76.

  28. US Vaccination Recommendation • Adolescents • 11-12 year of age and booster at 16 years • High risk conditions • 2-dose primary schedule – 2 months apart • Booster every five year • Exposure risk(microbiologist, travelers to endemic countries) • 1-dose primary schedule • Booster 3 years later (2-6 years of age) • Booster 5 years later (7 years of age or older) ACIP; MMWR; January 8, 2011;60(3):72-76.

  29. Guillain Barré Syndrome (GBS) • Passive surveillance suggested a possible association between GBS and MenactraTM • Two large studies in US using managed care organization data have not found any association • Past GBS no longer needs to be considered a precaution for MenactraTM Presentations by Velentgas and Weintraub to ACIP; June 2010.

  30. Provincial Schedules

  31. Provincial Schedules Canadian Nursing Coalition on Immunization (CNCI) as of April 19, 2011 http://www.phac-aspc.gc.ca/im/ptimprog-progimpt/table-1-eng.php

  32. Meningococcal A

  33. MenAfriVacTM • Conjugate meningococcal A vaccine for Sub-Saharan Africa meningitis belt • Meningitis Vaccine Project • Introduced into Burkina Faso, Mali and Niger in December 2010 with dramatic effects • Plans for Cameroon, Chad and Nigeria, then other countries • Given to 1-29 year olds • Cost less than 50 cents per dose • Estimated to prevent 1 million cases and save $300 million over the next decade http://www.meningvax.org/

  34. Meningococcal B

  35. Difficulties with Development • Capsule structurally identical to fetal brain cell adhesion molecules • Induce a weak immune response • Could involve production of autoantibodies • Outer-membrane-vesicle vaccine • Strain specific PorA, highly variable across strains • Each outbreak needs its own vaccine • Vaccines incorporate multiple PorAs

  36. Reverse Vaccinology • Take the genetic composition of the bacteria • Look for genes that may represent surface exposed proteins • Put into Escherichia coli expression system to make proteins • Mice immunized and antibodies assessed by serum bactericidal antibody (SBA) assay • Best candidate antigens made into vaccine

  37. Novartis Vaccine – Bexsero • Factor H binding protein (fHbp) – fusion protein • Neisserial heparin-binding antigen (NHBA) - fusion protein • Neisserial adhesin A (NadA) • Outer-membrane-vesicle New Zealand (OMVnz) • Aluminum adjuvant

  38. Immunogenicity • Needs to be assessed using serum bactericidal antibody (SBA) assays against various strains that express the target antigens • Evidence showing it is immunogenic at various ages and has an acceptable safety profile Bai et al. Expert Opin Biol Ther 2011

  39. Coverage of Strains • Because of the antigenic variation and different levels of expression of the proteins, need to assess how well the vaccine will protect against circulating strains • Meningococcal antigen typing assay (MATS) • ELISA measures cross-reactivity and quantity of the antigen • Correlates with serum bactericidal antibody (SBA) assay Donnelly J et al. PNAS Early Edition

  40. Coverage of Strains • Strains exceeded the threshold value for any of the three antigens had a ≥ 80% chance of being killed by SBA • MATS will allow for assessing expected strain coverage in various countries

  41. Pfizer Vaccine • Contains two factor H binding proteins, to cover various strains • In Phase II trials

  42. The Journey Continues ?? Questions ?? Thank You

More Related