Overview of seasonal Influenza Vaccines and Future Directions

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1 Overview of seasonal Influenza Vaccines and Future Directions San Jose, Costa Rica January 2013 Joseph Bresee Epidemiology and Prevention Branch Influenza Division National Center for Immunization and Respiratory Diseases CDC

2 Overview Influenza vaccines Types, composition Vaccine safety Vaccine effectiveness Vaccination strategies Risk-based vs. Universal vaccination Challenges and opportunities in the next few years

3 Seasonal Influenza Vaccines INFLUENZA VACCINES

4 Influenza Vaccines Best tool for preventing influenza Vaccines are component of multipart strategy for influenza control with hygiene, antivirals, quality medical treatment, NPIs

5 Clinical trials of inactivated vaccines Inactivated influenza vaccines have been available for decades Early development of vaccines was done by US military Extensive clinical trial data was collected in young, healthy military populations Outcomes were serologic evidence of infection or serologically confirmed illness, not prevention of influenza complications

6 Percent Protection 100 Efficacy of inactivated influenza vaccines, A(H1N1) 1943 B 1945 A(H1N1) 1950 A(H1N1) 1951 A(H1N1) 1953 B 1955 A(H1N1) 1957 A(H2N2) 1957 A(H2N2) 1958 B 1958 A(H2N2) 1960 A(H3N2) 1968 A( H3N2) 1969 Type of Virus, Year Courtesy A. Monto

7 Influenza Vaccines - overview Trivalent (H1N1, H3N2, B) Quadrivalent fomulations now or soon licensed that include 2 B virus antigens Annual vaccination required for optimal protection Antigenic changes in circulating strains Vaccine-induced antibodies wane over time Influenza vaccine programs: Conducted as seasonal campaigns (before local disease peaks) (Mostly) target persons at high-risk of severe outcomes 16

8 Approved seasonal influenza vaccines: types Inactivated vaccines Standard Inactivated vaccines Intradermal Inactivated vaccines High-dose Inactivated vaccine Adjuvanted inactivated vaccines Live attenuated vaccines

9 Influenza vaccines: types Standard Inactivated vaccines Many manufacturers Intramuscular injection 0.5cc per dose often decreased to 0.25cc for children 6-35 months Contains 15 µg hemagglutinin of each virus strain per 0.5cc dose 6 months of age or older products vary Protection primarily mediated by humoral immunity against the hemagglutinin protein Protection correlated with serum antibody levels postvaccination

10 Influenza vaccines: types Intradermal Inactivated vaccines Sanofi Pasteur Injected Intradermally using special syringe and needle Lower antigen content per dose (9 µg per virus strain) Lower volume (0.1cc) Licensed in US for y-o Potential advantages Acceptability among needlephobic persons Antigen-sparing Fluzone Intradermal Microinjection Syringe

11 Influenza vaccines: types High-dose Inactivated vaccine Sanofi Pasteur Intramuscular Injection 0.5 cc per dose Contains 60µg of each antigen per 0.5cc dose Licensed in US for >65 year-olds Advantages: better immune response may mean improved effectiveness in persons who respond poorly to standard dose vaccines (e.g. elderly) More injection-site reactions mostly mild

12 Influenza vaccines: types Live attenuated vaccines Medimmune; Russia; others in development Delivered by nasal spray or dropper o (0.2cc divided into each nostril) Nonpregnant, healthy individuals ages 2-49 years o Includes most HCWs o Excludes children 2-4 yrs with asthma or wheezing in last year Potential advantages: o Ease of use o No needles o Induction of broader immunity (cell-mediated); increased heterosubtypic protection o Potentially longer-lasting immunity o Superior effectiveness in children Limited availability

13 Seasonal Influenza Vaccines VACCINE EFFECTIVENESS

14 Vaccine effectiveness Effectiveness is variable from year to year and among populations Generally lower than routine EPI vaccines Factors that affect true vaccine effectiveness Antigenic relatedness between vaccine virus to circulating strains Host factors Age (immune responses in very young and very old) Underlying illnesses Vaccine type Programmatic issues

15 Influenza Vaccine efficacy if IIV in adults: meta-analyses Study Demicheli, et al (2000) Demicheli, et al (2009) Osterholm, et al (2012) No. studies reviewed Population Outcome VE 10 Adults Lab-confirmed influenza 38 Adults Lab-confirmed influenza y Lab-confirmed influenza 68 (49-79) 80 (56 91) [good match] 50 (27-65) [poor match] 59 (51-67)

16 Meta-analyses of influenza vaccine LAIV efficacy/effectiveness in children Reference No. studies / subjects Age range Study types Summary VE % Rhorer (2009) 9 / 27, m RCTs 72 Negri (2005) 6 / m 18 y RCT / Obs 80 (53-91) Jefferson (2008) 34 < 16 y RCT / Obs. 82 (71-89) Osterholm (2012) TIV 10 6m - 7 y RCT 83 (69-91) Jefferson (2008) 34 < 16 y RCT /Obs 59 (41-71) Negri (2005) 6 / m 18 y RCT / Obs 65 (45-77)

17 Vaccine effectiveness: special populations: Elderly persons Lower VE measured in elderly populations Studies difficult because RCTs rare because flu vaccine long-recommended in this group Confounding in observational studies Even so, well-done RCT and observational studies able to measure significant reductions in disease Only RCT of influenza vaccine VE in the elderly (Govaert et al. JAMA. 1994;272: ) Subjects: aged 60, generally healthy VE overall = 50% (CI: 39-65) years: 57% (CI: 33-72) >70: 23% (CI: )

18 Vaccine effectiveness: special populations: Pregnant Women Influenza vaccination of mothers during pregnancy effective in reducing influenza associated hospitalization of their infants <6 mos. Author Site/ Dates Design No. Vacc. No. Controls Effect in infants Zaman, 2008 Bangladesh (2004-5) RCT % ILI 69% lab + flu Poehling, 2011 USA (2002-9) Case- Control % hospitalization Eick, 2011 USA (2002-5) Prospective Cohort % lab-pos flu Benowitz, 2010 CAN/USA (2000-9) Casecontrol % hospitalized flu+

19 Indirect effects of influenza vaccination Monto JID, 1973 Tecumseh study From 1968 pandemic, vaccination of school children reduced illness in children and adults compared to town that did not vaccinate children Loeb JAMA 2009 Recent study of Hutterite communities in Canada Found 61% reduction in adult cases of influenza by vaccinating children Hospital-based HCP vaccination reduced nosocomial influenza Salgado, et al. Infect Control Hospital Epidemiol 2004 Health care worker vaccination in nursing homes reduces patient deaths Oshitani, et al; Potter, et al; Carmen, et al; Hayward et al. Referenced in HCP Vaccination MMWR November 25, 2011

20 Communication of influenza vaccine effectiveness is difficult

21 Estimates number of medically-attended illnesses averted by vaccinations, Year All ages 0-4 yrs 5-19 yrs yrs 65+ yrs , ,267 83, , , , ,611 82, , , ,252, , , , , , , , , , ,064, , , , ,891 Five Season Total 5,708,895 1,214,683 1,301,920 1,630,509 1,561,782 Illness/outcomes averted may be an easier and more meaningful way to communicate the value of the vaccine?

22 Seasonal Influenza Vaccines VACCINATION STRATEGIES

23 Influenza vaccines have been part of U.S. public health programs since 1960 Burney LE. Public Health Rep Oct;75(10):944

24 Influenza vaccination recommendations over time Before 2000: Persons aged 65 or older Persons with high-risk chronic medical conditions Pregnant women in the second or third trimester Household contacts of the above Health care workers 2000: Adults 50 and older 2004: Children aged 6 23 months Household contact of children aged months Women who will be pregnant during influenza season 2006: Children aged 6 59 months Household contacts of children aged 0 59 months 2008: All children aged 6 months 18 years 2010: All persons > 6 months in the US

25 Seasonal Influenza Vaccines CHALLENGES AND NEXT STEPS

26 Challenges Expanding or introducing influenza vaccine programs is challenging: Variety of vaccine products/types Developing policy requires a solid evidence base (e.g. risk groups, timing of campaign) Most risk groups are not those targeted by routine EPI vaccines new partners, training, etc. Communicating value is complicated Need for annual vaccination

27 Gaps Most partners need education on the need / value of the vaccine Relative benefit of annual campaigns in countries with substantial year-round disease is poorly understood Relatively few data on the performance of vaccine in developing country populations Disease burden and economic burden (or CE of vaccine) poorly understood in many places (but data being generated quickly) NRAs gaining experience with approval of influenza vaccines

28 Opportunities New developers and producers of influenza vaccines Capacity has increased dramatically and will continue to Interest in influenza prevention post-pandemic Will wane quickly though Substantial and high quality surveillance and disease burden data now available for most countries New WHO SAGE recommendations to use vaccine

29 THANK YOU