the science of influenza vaccine development: implications for the public health practitioner david...
TRANSCRIPT
![Page 1: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/1.jpg)
The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner
David Cho, PhD, MPH
Program Officer, Influenza Vaccine Development
Respiratory Disease Branch, DMID, NIAID
![Page 2: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/2.jpg)
Goals of the Presentation
Describe the basic scientific differences between seasonal and pandemic influenza
Explain what researchers are doing to overcome the challenges that a pandemic strain brings
Explain what practitioners should consider in preparation for a pandemic
![Page 3: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/3.jpg)
Characteristics of a Pandemic Influenza Virus
Influenza A virus with a novel hemagglutinin or novel hemagglutinin and neuraminidase in man
Susceptibility (no neutralizing antibody) to the novel virus in a large proportion of the population
Demonstration of the virus to cause and spread person-to-person in a sustained fashion
![Page 4: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/4.jpg)
Influenza Virus Nomenclature
Source: Subbarao/Murphy
![Page 5: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/5.jpg)
Clinical Burden of Influenza Virus Morbidity and Mortality
Previous pandemics
1918 H1N1 transferred from birds?: > 40 million deaths worldwide
1957 H2N2 avian-human reassortant: > 2 million deaths
1968 H3N2 avian-human reassortant: > 1 million deaths
Seasonal influenza
Millions of human cases; hundreds of thousands of hospitalizations yearly in the US alone
Influenza and pneumonia: 7th leading cause of mortality in the US in 2002
20,000 to 40,000 deaths annually US
250,000 to 500,000 deaths annually worldwide
![Page 6: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/6.jpg)
Clinical Burden of Influenza Virus Morbidity and Mortality (continued)
H5N1 Avian influenza
290+ documented human cases
170+ deaths
Over 3 ½ + years, fewer than 100 documented cases/ year
Seasonal influenza Millions of human cases;
hundreds of thousands of hospitalizations yearly in the US alone
Influenza and pneumonia: 7th leading cause of mortality in the US in 2002
20,000 to 40,000 deaths annually US
250,000 to 500,000 deaths annually worldwide
![Page 7: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/7.jpg)
Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO 11 April 2007
Country cases deathsAzerbaijan 8 5
Cambodia 7 (1) 7 (1)
China 24 (2) 15 (1)
Djibouti 1 0
Egypt 34 (16) 14 (4)
Indonesia 81 (6) 63 (5)
Iraq 3 2
Lao People’s Dem Rep 2 2
Nigeria 1 1
Thailand 25 17
Turkey 12 4
Viet Nam 93 42
Total 291 172
Cases and countries shown in gold for events since January 2007. WHO reports only laboratory-confirmed cases.
> 50% mortality
![Page 8: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/8.jpg)
![Page 9: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/9.jpg)
Mississippi Americas flyway
Pacific Americas flyway
Atlantic Americas flyway
East Atlantic flyway
Central Asia flyway
East Asia/ Australian flyway
East Africa West Africa flyway
Black Sea/ Mediterranean flywayDistricts with
H5N1 outbreaks since January 2005
Sources: AI outbreaks: OIE, FAO, and Government sources. Flyways: Wetlands International
H5N1 outbreaks in 2005 and major flyways of migratory birds(situation on 30 August 2005)
![Page 10: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/10.jpg)
Influenza A subtypes: 16 Hemagglutnins (HA) 9 Neuramindases (NA)
All subtypes: endemic in birds
H1N1, H2N2, H3N2: endemic in people
HA trimers: Binds sialic acid and fuses viral and cell membranes
NA tetramers: Removes sialic acid to prevent adherence to self or cell during budding
Schematic Version of Influenza Virus (continued)
![Page 11: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/11.jpg)
Schematic Version of Influenza Virus (continued)
RNA Polymerases (PB1, PB2, PA) attached to each RNP
Nucleoprotein (NP) binds RNA and Matrix protein (M1)
On viral and infected cell surface:
M2 tetramers Hydrogen ion channel
In infected cell: NS1 Binding host proteins Role in IFN resistance
![Page 12: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/12.jpg)
Emergence of New Human Influenza Subtypes
![Page 13: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/13.jpg)
H5N1 Virulence Factors in Mammals
HA with multibasic amino acid motif (RERRRKKR) at the HA1-HA2 cleavage site
Polymerase genes adapted to mammalian host 1997 H5N1 with PB2 lysine at AA position 627
2004 H5N1 with polymerases from human source more virulent in ferrets than same H5N1 with polymerases from avian source
NS1 gene adapted for mammalian host Inhibition of interferons
Increased TNF alpha
Source: Salomon et al. JEM 2006;203:689.
![Page 14: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/14.jpg)
What Makes the HA Highly Pathogenic?
Source: Horimoto and Kawaoka. Nature Reviews Microbiology, 2005
![Page 15: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/15.jpg)
Questions?
![Page 16: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/16.jpg)
Common Features of H5N1 in Humans
Contact with sick/dying poultry
Frequently healthy young person Average age <18
Incubation period 2–4 days from probable exposure
Presenting symptoms fever, dyspnea, cough
Diarrhea more common than expected with influenza
Leukopenia/lymphopenia/thrombocytopenia
Metabolic abnormalities
![Page 17: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/17.jpg)
Common Features of H5N1 in Humans (continued)
High frequency of progressive pneumonia Mostly primary viral
Occasional contribution of bacteria?• (Staphylococcus aureus and Haemophilus
influenzae)
Hepatic necrosis and acute tubular necrosis
High mortality rate in spite of antiviral/steroid/antibacterial treatment
![Page 18: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/18.jpg)
Common Features of H5N1 in Humans (continued)
Diffuse activation of the innate immune system (“cytokine storm”) with increased levels of: Interleukin 1 beta
Interleukin 6
Interleukin 8
Tumor Necrosis Factor alpha
Interferon alpha
Interferon gamma
Interferon inducible protein 10
Soluble Interleukin 2 receptor
Monocyte chemoattractant protein 1
![Page 19: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/19.jpg)
Source: Tran et al. N Engl J Med 350:1171, 2004
Chest Radiographs of Patient with Severe H5N1 Influenza Pneumonia: Vietnam, 2004
![Page 20: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/20.jpg)
Additional H5N1 Virulence Factors in Humans
HA receptor binding
Two ketosidic linkages of sialic acid to galactose: alpha 2,3 and alpha 2,6
Avian HA preference for alpha 2,3 linkage
Human upper airway predominantly alpha 2,6 linkage
Human lower airway more abundant in alpha 2,3 linkage
Possibly contributes to the high incidence of primary viral pneumonia caused by H5N1 viruses
Source: Shinya et al. Nature 2006;440:435
![Page 21: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/21.jpg)
Evidence for Person-to-Person H5N1 Transmission (Not Sustained)
Possible instances of infection of health care workers during 1997 outbreak in Hong Kong
Family clusters Vietnam, Thailand* and Indonesia**
Cluster in Indonesia suggests human to human to human transmission before the chain extinguished***
(* Ungchusak et al. N Engl J Med 2005;352:333-340
** Kandun et al. N Engl J Med 2006;355:2186-2194
***Normile Science 2006;312:1855)
![Page 22: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/22.jpg)
Detection of H5N1 Viruses: Lessons from Recent Experiences Throat samples may give higher yield than nasal samples,
but both worth examining Rapid tests poor negative predictors and lack specificity
But microarray methods improving and may provide sensitivity and specificity
Polymerase chain reaction (PCR) increases sensitivity but success depends on the primers used for amplification
Laboratory confirmation generally accepted Viral culture Positive PCR for H5N1 RNA
• (see www.cdc.gov/mmwr/preview/mmwrhtml/mm5505a3.htm) Positive immunofluoresence using a monoclonal
antibody for H5 4-fold or greater rise in H5-specific antibody in
paired acute and convalescent sera
![Page 23: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/23.jpg)
Questions?
![Page 24: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/24.jpg)
Antiviral Therapies for Influenza
![Page 25: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/25.jpg)
Antiviral Agents for Treatment of H5N1 Viruses
Early treatment recommended for suspect cases but efficacy, optimum dose, and duration uncertain
Treatment of choice is a neuraminidase inhibitor Oseltamivir has been most frequently used
• 5 days treatment of 75 mg twice daily for adults and dose decreases for children dependent on body mass is standard
• Higher doses may be considered by some authorities but no prospective studies
Oseltamivir resistance during treatment may not result in resistance to zanamivir
![Page 26: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/26.jpg)
Antiviral Agents for Prophylaxis of H5N1 Viruses
Oseltamivir 75 mg once daily for 7–10 days may be considered for significant post exposure prophylaxis
But rationale is based on evidence from studies with other influenza A virus subtypes
Potential recipients would be poultry workers/cullers, health care workers, household contacts
![Page 27: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/27.jpg)
Antiviral Agents for Treatment of H5N1 Viruses
Zanamivir administered as inhaled powder, which may be difficult with respiratory symptoms
Amantadine/rimantadine resistance common in Asian H5N1 viruses Possibly from agricultural use of drugs
Amantadine/rimantadine susceptibility of some recent strains (African/European/Middle East) May be clade specific May be a role for M2 inhibitors
Other drugs (ribavirin and interferon) may also be considered but no value clearly documented
Clinical studies in progress Peramivir (injectable neuraminidase inhibitor) CS8958 (once daily neuraminidase inhibior) 705 (polymerase inhibitor) Studies may start soon with FluDase (sialidase to remove viral receptors)
![Page 28: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/28.jpg)
Pandemic Influenza Preparedness: Complementary Roles Within DHHS
![Page 29: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/29.jpg)
![Page 30: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/30.jpg)
Adults (18 – 64y; 7.5, 15, 45, 90ug)*
Immune response observed at all dose levels after a single dose, unadjuvanted vaccine
2 x 90mcg doses produced most frequent and highest antibody responses
April 17, 2007 FDA approval of sanofi vaccine at 90 mcg dose for persons exposed to H5N1
Additional studies in elderly (65y+; 45 or 90ug); children (2–9y; 45ug)
Immunogenicity results similar to adults
(* Treanor et al. N Engl J Med 2006; 354:1343-1351)
Adults (18 – 64y; 7.5, 15, 45, 90ug)*
Immune response observed at all dose levels after a single dose, unadjuvanted vaccine
2 x 90mcg doses produced most frequent and highest antibody responses
April 17, 2007 FDA approval of sanofi vaccine at 90 mcg dose for persons exposed to H5N1
Additional studies in elderly (65y+; 45 or 90ug); children (2–9y; 45ug)
Immunogenicity results similar to adults
(* Treanor et al. N Engl J Med 2006; 354:1343-1351)
NIH Trials with sanofi pasteur H5N1 A/Vietnam/1203/2004
![Page 31: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/31.jpg)
![Page 32: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/32.jpg)
Controlled trials completed or planned CSL Australia: subvirion vaccine +/- AlPO4
Baxter Austria: whole virus +/- AlOH
Novartis UK: subunit vaccine +/- AlOH
Sanofi France and US: subvirion vaccine +/- AlOH in adult and elderly populations
Summary Vaccines well tolerated with or without aluminum
adjuvant
Immunogenicity: Aluminum adjuvants do not show a clear advantage over vaccine alone
Controlled trials completed or planned CSL Australia: subvirion vaccine +/- AlPO4
Baxter Austria: whole virus +/- AlOH
Novartis UK: subunit vaccine +/- AlOH
Sanofi France and US: subvirion vaccine +/- AlOH in adult and elderly populations
Summary Vaccines well tolerated with or without aluminum
adjuvant
Immunogenicity: Aluminum adjuvants do not show a clear advantage over vaccine alone
Dose Optimization of Inactivated H5N1 Vaccines: Aluminum Adjuvants
![Page 33: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/33.jpg)
Trials with other adjuvants
GSK: subvirion vaccine +/- AS (proprietary adjuvant system)
Novartis UK: subunit vaccine with MF59 (proprietary adjuvant system
Summary
Vaccines well tolerated with or without adjuvant but somewhat increased local reactogenicity
Immunogenicity: Adjuvants result in more frequent and higher antibody responses
Trials with other adjuvants
GSK: subvirion vaccine +/- AS (proprietary adjuvant system)
Novartis UK: subunit vaccine with MF59 (proprietary adjuvant system
Summary
Vaccines well tolerated with or without adjuvant but somewhat increased local reactogenicity
Immunogenicity: Adjuvants result in more frequent and higher antibody responses
Dose Optimization of Inactivated H5N1 Vaccines: Other Adjuvants
![Page 34: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/34.jpg)
![Page 35: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/35.jpg)
Trials with other alternate route of administration
Sanofi subvirion vaccine given intradermal (ID) at reduced dose or intramuscular (IM) at higher dose
Summary
Vaccines well tolerated but increased local reactogenicity with intradermal administration
Immunogenicity: High doses IM more immunogenic than lower doses ID
Additional studies planned for better direct comparison of same dose given ID and IM
Trials with other alternate route of administration
Sanofi subvirion vaccine given intradermal (ID) at reduced dose or intramuscular (IM) at higher dose
Summary
Vaccines well tolerated but increased local reactogenicity with intradermal administration
Immunogenicity: High doses IM more immunogenic than lower doses ID
Additional studies planned for better direct comparison of same dose given ID and IM
Dose Optimization of Inactivated H5N1 Vaccines: Route
![Page 36: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/36.jpg)
Source: The WHO Global Influenza Program Surveillance Network
![Page 37: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/37.jpg)
Clade 1 vaccine; trials underway Vaccine candidates: A/VN/1203/2004 and A/VN/1194/2004
Clade 2 - subclade 2 candidates available; vaccine production ongoing CDC: Indonesia/05 (Sanofi US; DHHS) NIBSC: A/Turkey/Turkey/1/05
St. Jude: A/BHG/Qinghai Lake/1A/2005 and A/WS/Mongolia/244/05
Clade 2 - subclade 3 candidates in development CBER/FDA: A/Duck/Laos/3295/06 CDC: A/Anhui/1/2005 St. Jude: A/Japanese White Eye/HK/1038/06
Clade 1 vaccine; trials underway Vaccine candidates: A/VN/1203/2004 and A/VN/1194/2004
Clade 2 - subclade 2 candidates available; vaccine production ongoing CDC: Indonesia/05 (Sanofi US; DHHS) NIBSC: A/Turkey/Turkey/1/05
St. Jude: A/BHG/Qinghai Lake/1A/2005 and A/WS/Mongolia/244/05
Clade 2 - subclade 3 candidates in development CBER/FDA: A/Duck/Laos/3295/06 CDC: A/Anhui/1/2005 St. Jude: A/Japanese White Eye/HK/1038/06
Keeping up with H5N1 Drift: Vaccine Reference Virus Efforts Underway
![Page 38: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/38.jpg)
Questions?
![Page 39: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/39.jpg)
What Can We Expect of H5N1 Influenza?
Since 2003, increasing number of countries in Africa, Asia, and Europe have documented H5N1 virus in poultry or migratory birds.
Continued H5N1 evolution, possibly amplified by uncontrolled transmission in high-density poultry.
Human cases track exposure to infected poultry and are accelerating in frequency.
Clusters and potential human-to-human spread plus epidemic influenza provide continuing chance for reassortment.
![Page 40: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/40.jpg)
Hong Kong model for eliminating infected poultry and preventing human illness
Agricultural surveillance and action are critical early steps.
Enforcement of market sanitation.
Poultry segregation (quail as asymptomatic carriers eliminated).
Vaccination with agricultural vaccine (asymptomatic infections possible).
Difficult to implement because of social and economic concerns.
![Page 41: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/41.jpg)
Annual Influenza Vaccine Production
Coordinated collaborative
&complex!
PHSstrain
selection
Global surveillance
(ongoing)
WHO strain
selection
Generation of highyield reassortants
“candidates”
FDA release testing
FDA potencyreagents
Filled into vials/syringes
FDA approvessupplement to
license
Formulated lots
Sheep sera
Millions of fertilized
eggs
Standardantigen
Millions of chickens
Bulk vaccine
production
~1 rooster for 10 hens
Antigenic relatednessconfirmed
Distribution/vaccine use
PurifiedHA
Manufacturersassess growth &
yield of candidates
? Demand
? Severity of Season
? Recommendations
Future:
revers
e
genetics
technology
![Page 42: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/42.jpg)
Influenza Vaccine Production Timeline
![Page 43: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/43.jpg)
U.S. Seasonal Influenza Vaccine: Production and Use
![Page 44: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/44.jpg)
Beyond Eggs and Cell Culture: Research Efforts to Develop New Technologies
Goal: Develop “agile” vaccine platformsDNA
Plasmids – single or multiple gene combinations (HA + NP + M2); conserved regions; single subtype or multiple subtypes (H3 + H1 + H5)
VectorAdenovirus, alphavirus, salmonella strains
Recombinant subunitExpression systems, baculovirus, drosophila
Peptide vaccinesSynthesized multigenic peptides
Vector-based vaccines
![Page 45: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/45.jpg)
Influenza Virus and Protein RNAs: Targets for a “Universal Vaccine”
Source: Subbarao/Murphy
![Page 46: The Science of Influenza Vaccine Development: Implications for the Public Health Practitioner David Cho, PhD, MPH Program Officer, Influenza Vaccine Development](https://reader035.vdocuments.net/reader035/viewer/2022081516/56649e195503460f94b054a1/html5/thumbnails/46.jpg)
Seasonal Influenza
Preparedness
Pandemic Influenza
Preparedness