Influenza Vaccines Where Are We and What’s Ahead Vermont Immunization Conference October 28, 2011

1. Influenza VaccinesWhere Are We and What’s AheadVermont Immunization ConferenceOctober 28, 2011 Brant Goode, RN/BSN, MPH CDC Career Epidemiology Field Officer

2. Neither I nor any of my immediate family members have financial relationships or interests with entities producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Opinions and perspectives presented are my own and while based on professional experience and education are not endorsed by CDC or VDH. Claim I am directly interested in assuring that scientific approaches help inform public health policy decisions. Disclaimer Vermont Department of Health

3. Initial Objectives Review influenza fundamentals (5 min.) Review current immunization practices (5) Define three lessons from 2009 pan flu H1N1 (5) Describe influenza immunization coverage in VT (10) Define barriers and approaches to overcoming them (15) Describe future directions, approaches to influenza immunization (15) Vermont Department of Health

4. Current Objectives Briefly describe influenza, its epidemiology and the public health efforts to reduce its burden Vaccine coverage in US—progress and lack thereof Lessons from 2009 pandemic influenza A H1N1 Current Vaccine Practices SEE DR. ATKINSON’S SLIDES Discuss future of vaccines for flu Return the present while we look to the future Vermont Department of Health

5. Influenza in brief Acute viral illness • Fever, respiratory, constitutional features Rapid incubation Spreads primarily through respiratory droplets • Esp. during acute phase, 24-48 hours Notable for seasonality, occasional pandemics • Approx. 18-20 million excess Acute Febrile Respiratory Illnesses each year* Deaths due to complications well-known; primary influenza less so • P & I mortality: Usually expressed in 1,000s to 10,000s/yr with wide ranges • Elderly, immunocompromised • Infants and children Prevention and treatment • Vaccines • Distance between infected persons and susceptible hosts • Antimicrobials • Care and Comfort *Sullivan et al, Estimates of the US Health Impact of Influenza, AJPH 1993 (83;1712-1716)

6. Seasonal Influenza Vaccination Coverage by Age: 2009-10 and 2010-11 Seasons 1. BRFSS 2008-09 for adults; child estimate from 2009 NHIS, ages 6 mo. – 18 years, online at: www.cdc.gov/vaccines/stats-surv/nhis/2009-nhis.htm. 2. BRFSS and National 2009 H1N1 Flu Survey (NHFS) estimates, 2009-10. Online at: www.cdc.gov/flu/professionals/vaccination/coverage_0910estimates.htm. 3. BRFSS and NIS estimates, 2010-11. Online at: www.cdc.gov/flu/professionals/vaccination/coverage_1011estimates.htm -From James Singleton, Influenza Vaccination Distribution and Coverage, United States, 2010-11 and 2011-12 Seasons, presentation to ACIP, October 2011.

7. Place of Influenza Vaccination Among Adults – United States, 2010-11 SeasonMMWR June 17, 2011;60(23):781-785 BRFSS, January-March 2011 data from 46 states and District of Columbia

8. Pandemic Lessons Vermont Department of Health

9. Planning Can Help

10. Classification by Timing and Severity Vermont Department of Health

11. How Did the Pandemic Vaccination Effort Work? Vermont Department of Health

12. Reed et al,Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009* Some degree of pre-existing serologic cross-reactivity to pH1N1 noted in older adults A single cross-sectional serologic survey won’t distinguish recent infection from prior infection with similar historic H1N1 viruses Immunity from pH1N1 vaccination not serologically distinguishable from immunity due to natural infection So what role did pH1N1 vaccination play? *Presentation at 2011 Council of State and Territorial Epidemiologists

13. Methods: Baseline (pre-pandemic) seroprevalence survey using NHANES (2007-2008) 2009 serosurvey Used serum leftover from routine testing (Dec 15, 2009-January 15, 2010) Obtained from commercial diagnostic laboratories in a US state in each of 10 HHS regions Age-stratified: 6 age groups Adjusted for contributions of various sources of seropositivity Vaccine coverage by week: BRFSS, NHFS (’09-’10) % Influenza-like illness (ILI) from sentinel sites by week Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

14. Graphically speaking TOTAL POPULATION Cross-reactive Ab Seropositivity, 2009 2007-08 NHANES pH1N1 vaccine Estimates of pH1N1 vaccine coverage in the US by state during the study period Natural infection Estimated incidence of pH1N1 infection Sensitivity / Specificity Laboratory analysis* *Veguilla et al. J ClinMicrobiol2011; 49:2210 Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

15. Results: Nationwide ILI activity and pH1N1 vaccination coverage Period of sera collection Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

16. Results: Seropositivity to A/California/7/2009 * Age-standardized to 2009 US population Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

17. Results: Increase in seroprevalence * Age-standardized to 2009 US population ** Adjusting for: baseline cross-reactive immunity, pH1N1 vaccine coverage, sensitivity/specificity of the assay Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

18. Estimated prevalence of seropositivity to pH1N1 by source through 2009, by age group * Total is age-standardized to 2009 US population Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

19. So what did vaccine accomplish? High population immunity by December 2009, especially in children ~ 25% of the US infected with pH1N1 during the spring and fall waves >50% of school-age children Many persons remain susceptible to future infection Difficult to interpret serology in the elderly Increased level of cross-reactive antibody Questions about long-term immunity to influenza Reed et al, Prevalence of seropositivity to 2009 pandemic influenza A/H1N1 virus infection in the US by December 2009

20. Influenza Vaccination—Challenges Annual updates, annual (re-)vaccination Public perceptions Health care provider perceptions Vermont Department of Health

21. Meeting the Challenges—What’s Ahead? Better vaccines Efficacy Route Frequency needed Vermont Department of Health

22. Influenza Vaccines—Milestones 1943: Chemically killed whole viruses grown in eggs 70% efficacy Improved purification, production, targeting 1969: Reassortant strains—genetic manipulation mass production 1980: Reverse engineering to combine wild and lab strains for still easier production Still egg-based production 2002: Candidate vaccine for Avian influenza 2004: entire segments for vaccine engineered without use of complete seed strains: “Mix and Match” More recently: LAIV—cold adapted Selected references: Francis et al. Protective effect of vaccination against influenza A. Proc Soc Exp Biol Med 1944;55:104-405. Quadros ed. Vaccines: preventing disease and protecting health. Pan American Health Organization 2004. Kilbourne ED. Bulletin of the World Health Organization. 1969. 41:643-645. Subbarao et al. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology 2003; 305:192-200.. Shi et al. Generation of an attenuated H5N1 avian influenza virus vaccine with all eight genes from avian viruses. Vaccine 2007; 25:7379-84. Nolan et al. Safety and immunogenicity of a live-attenuated influenza vaccine blended and filled at two manufacturing facilities. Vaccine 2003 21:1224-1231. Vermont Department of Health

23. Influenza Vaccines—Milestones 2011: Search for and identification of broadly neutralizing monoclonal antibodies (mAb) from cells of donors who produced strong responses against a broad range of viruses. A person who contracted the strain of influenza responsible for the 2009–10 pandemic produced an antibody with the remarkable ability to block all strains of influenza A. The mAb binds to a conserved region on the hemagglutinin molecule. -Corti et al. A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins. Science; published Online July 28 2011: 1205669. Milestones we’d like to see: A flu vaccine that elicits “super-antibodies” against a broad range of viruses One that produces longer protection so dose frequency is reduced Easy administration Well-accepted by public When? We’ll see! Vermont Department of Health

24. What’s Ahead: Summary Candidate criteria for influenza vaccines Broader coverage Longer duration of protection More acceptable to public and HCPs Timeline Better as scientific advances continue Roles for HCPs and Public Health Continue current efforts Awareness of strengths, limits and appropriate indications for vaccines will position you to address questions and concerns Look forward to improvements Vermont Department of Health

25. This year and next… Watch and share the official flu news Be good consumers of information Be good at sharing good information Vermont Department of Health

26. Influenza Info for Vermont Health Care Providers: healthvermont.gov/prevent/flu/flusurveillance.aspx Vermont Department of Health

27. www.cdc.gov/flu/weekly/index.htm Vermont Department of Health

28. Thank you Brant Goode, RN/BSN, MPH brant.goode@state.vt.us 802-865-7707 Vermont Department of Health