New Recommendations for Meningococcal Vaccines

1. New Recommendations for Meningococcal Vaccines Amanda Cohn, MD Division of Bacterial Diseases/NCIRD ACIP Working Group Meeting June 8, 2009 Presentation for working group not what we are planning to present to ACIP Draft – Do not circulatePresentation for working group not what we are planning to present to ACIP Draft – Do not circulate

2. Outline Recommendations for Revaccination Persons at “prolonged” increased risk Evidence to support need for booster Immune response and safety after revaccination Licensure of MenACWY-CRM Second vaccine for use in adolescents Comparison to MCV4-D

3. 2005 Statement: Revaccination after MCV4 MCV4 licensed as a single dose “ACIP expects that MCV4 will provide longer protection than MPSV4; however, studies are needed to confirm this assumption. More data will likely become available within the next 5 years to guide recommendations on revaccination for persons who were previously vaccinated with MCV4.”

4. Revaccination with meningococcal polysaccharide vaccine (MPSV4) “Revaccination might be indicated for persons previously vaccinated with MPSV4 who remain at increased risk for infection.” Children (age <4 years) should be considered for revaccination after 2--3 years For older children and adults, revaccination might be considered after 5 years Accepted standard of care for high-risk groups

5. Proposed 2009 definition: “Prolonged” high-risk Increased risk of infection Persistent complement deficiency Anatomic or functional asplenia Suboptimal response to vaccination Anatomic or functional asplenia Prolonged or frequent exposure Microbiologists who are routinely exposed to isolates of N. meningitidis Frequent travelers to or people living in areas with high rates of meningococcal disease (Meningitis belt)

6. How many people fall into a prolonged high-risk group About 60,000 persons with sickle-cell disease in the United States Unknown prevalence of complement deficiencies Approximately 20,000 doses annually to groups in high-risk only age groups* 4,000 2-10 year-olds 15,000 19-59 year-olds

7. Rationale for not including college freshmen or military recruits Larger cohort (>600,000 a year) and broad implications for revaccination In 2009, very few persons in these groups vaccinated >5 years prior Coverage 11% for 13 year-olds in Fall 2006 High vaccination coverage among college freshmen and military recruits Potential for herd immunity in this setting No assessment of degree of transmission in highly vaccinated populations

8. Why do we think there is a need for a booster in high-risk persons? Serum Bactericidal Activity (SBA) Measure of ability of sera to kill a strain of N. meningitidis in the presence of complement Accepted marker of protection Conjugate properties vs. circulating antibody Contribution of each to protection unknown Memory alone not sufficient to protect against meningococcal disease Lack of herd immunity in the U.S. population to protect high-risk individuals

9. SBA-BR seroresponse =1:128 post-vaccination, serogroup C

10. Antibody persistence 3 years after MCV4, serogroup C

11. Safety and Revaccination Safety based on limited data and unlimited expert opinion Results of small studies (<120 participants with prior MCV4) are reassuring with similar safety profiles post-vaccination compared to participants naïve to MCV4. Risk-benefit in favor of revaccination High morbidity and mortality of disease, especially among persons with late complement deficiency or asplenia

12. SBA-BR seroresponse =1:128 : Serogroup C

13. MCV4 vs. MPSV4 in children 2–10 Years of age (GMTs): Serogroup C

14. Optimal timing of revaccination: Children aged 2-6 years Limited antibody persistence data with MCV4 suggests children vaccinated at age 2-3 years not protected 3 years post-vaccination Children at increased risk in this age group likely to be asplenic Suboptimal response to vaccine Additional dose 2-3 years after first MCV4 may benefit this small group

15. Rationale for revaccination recommendations Abundance of caution Demonstrated disease risk Low-risk for adverse events Limited off-label use, small group targeted Evidence of waning functional antibody High levels important for persons with complement deficiency, asplenia Not protected by herd immunity in population Evidence of boost response to revaccination

16. Revaccination Recommendation- June 2009 Persons who previously were vaccinated at age =7 years and are at prolonged increased risk should be revaccinated 5 years after their previous meningococcal vaccine Persons who previously were vaccinated at ages 2--6 years and are at prolonged increased risk should be revaccinated 3 years after their previous meningococcal vaccine Persons who remain in one of these increased risk groups indefinitely should continue to be revaccinated at 5-year intervals

17. Recommendation #2 Because of the limited period of increased risk, ACIP currently does not recommend that college freshmen living in dormitories who were previously vaccinated with MCV4 be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 =5 years previously are recommended to be vaccinated with MCV4.

18. Licensure of MenACWY-CRM (Menveo), February 2010 Quadrivalent meningococcal conjugate vaccine Same serogroups as Menactra Licensed for ages 11-55 years Not for use in 2-10 year-olds Used in same recommended groups aged 11-55 years as Menactra

19. Lyophilized serogroup A, reconstituted with serogroups C, W, and Y

20. Guillain-Barré syndrome and MCV4 and MenACWY-CRM Menactra Package Insert: “Guillain-Barré syndrome (GBS) has been reported in temporal relationship following administration of Menactra vaccine … Persons previously diagnosed with GBS should not receive Menactra” Menveo Package Insert: “Following vaccination with a U.S.-licensed meningococcal quadrivalent polysaccharide conjugate vaccine, an evaluation of post-marketing adverse events suggested a potential for an increased risk of Guillain-Barré Syndrome (GBS)(1). Data are not available to evaluate the potential risk of GBS following administration of MENVEO.”

21. Current ACIP Position, MMWR, Aug 2007 Guillain-Barré syndrome (GBS) has been associated with receipt of MCV4. Persons with a history of GBS might be at increased risk for postvaccination GBS; therefore, a history of GBS is a relative contraindication to receiving MCV4. Persons recommended to receive meningococcal vaccination who have a history of GBS (or their parents) should discuss the decision to be vaccinated with their health-care provider . MPSV4 can be used for short-term protection.

22. Upcoming meningococcal vaccine ACIP topics Use of meningococcal conjugate vaccines in infants Update on post-licensure surveillance for GBS among recipients of MCV4 Consideration for revaccination of adolescents who are entering college Updated ACIP Statement Standardization of nomenclature

23. References Revaccination Notice to Readers, MMWR September 2009 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5837a4.htm Menveo Licensure, MMWR March 12 2010 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a5.htm Prevention and Control of Meningococcal Disease http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm

24. Thank you! Amanda Cohn, MD Meningitis and Vaccine Preventable Diseases acohn@cdc.gov