how vaccine have been managing new type of diseases in human history, and its social and economic...
TRANSCRIPT
How Vaccine Have Been ManagingNew Type Of Diseases In Human History,And Its Social And Economic Benefits
June 18, 2015
Cem Özesen, M.DMedical Director, MSD Korea
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Agenda
• Vaccine Development; History and Impacts
– Case I; HPV Vaccine
– Case II; Ebola Virus
• Closing
• ~ 430 B.C: Peloponesian War, Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time
• 15th centurry: Chinese and Turks use dried crusts of smallpox as ”vaccine”
• 1798: Edward Jenner – smallpox vaccine
History of Vaccine
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1798 1885 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2008
Smallpox
Rabies
TyphoidCholera
DiphtheriaPertussis
Tetanus
Influenza
Rickettsia
DTwP DTaP
IPV
OPV
Measles
MMR
Varicella
Rubella
Hib
HBV
BCG
Meningococcus
Pneumococcus
JEV PCV
MCV
HPV
RotavirusZoster
BCG (Bacille Calmette-Guerin vaccine)JEV (Japanese enthephalitis vaccine)DTwP (Diphtheria, Tetanus, whole cell per-tussis)DTaP (Diphtheria, Tetanus, acellular pertus-sis)IPV (Inactivated polio vaccine)OPV (Oral polio vaccine)MMR (Measles, Mumps, Rubella)Hib (Haemophilus influenzae type b vaccine)HBV (Hepatitis B vaccine)PCV (Pneumococcal conjugate vaccine)MCV (Meningococcal conjugate vaccine)HPV (Human papillomavirus vaccine)
History
History of Vaccine Development
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References: 1. Centers for Disease Control and Prevention. Ten Great Public Health Achievements — United States, 1900–1999 . Morbidity and Mortality Weekly Report (MMWR).1999; 48(12): 241-264.;2. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Washington, DC: Public Health Foundation; 2012.;3. WHO, UNICEF, World Bank. State of the World’s Vaccines and Immunization, 3rd ed. Geneva, World Health Organization; 2009.; 4. World Health Organization. Immunization Coverage. April 2013; Fact Sheet 378. http://www.who.int/mediacentre/factsheets/fs378/en. Accessed February 19, 2014.
2 to 3 millionlives are saved worldwide each year
through vaccination4
According to the World Health Organization, vaccines help
prevent more than common infectious diseases3 30
Vaccine,from treatment to prevention
• Vaccines are one of the greatest public health success stories of the last two centuries,
• eradicating smallpox1 and nearly eliminating other diseases like polio worldwide.2
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Vaccine Preventable Diseases
• Tuberculosis
• Diphtheria
• Pertussis
• Tetanus
• Polimyelitis
• Measles
• Mumps
• Rubella
• Japanese en-cephalitis
Decreased Incidence of Vaccine Preventable Diseases in Korea (~2006)
Impact of vaccines in Korea
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Recent Trends in Vaccine
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• Adult Vaccines (Zoster vaccine, Pneumococcal vaccine, Influenza) • Vaccine for cancer prevention (HPV Vaccine)• New vaccines for Viral disease (Rota Virus, Ebola, Dengue, etc)• Expansion of vaccine type coverage (4vHPV ->9vHPV)
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MSD licenses first measles vaccine in the US
1963
MSD’s Dr. Hilleman isolates the mumps virus to create the first mumps vaccine
M-M-R® trivalent vaccine introduced
1971
1995
2005
1960s
MSD licenses the first vaccine against mumps
1967
MSD licenses the first vaccine against rubella
1969
1970s
MSD licenses a vaccine against pneumococcal disease
1977
1981
1983
1978
1980s
1986
1990s 2000s
2006
First plasma-derived hepatitis B vaccine licensed, Heptavax-B (Hepatitis B Vaccine)
1996
1990
1890s
1898
H.K. Mulford Co. introduces its smallpox vaccine
* MSD and its predecessor companies have a history with vaccines that dates back more than 100 years. In 1898, the H. K. Mulford Company pro-duced its first batch of smallpox vaccine. In 1929, the H. K. Mulford Company was purchased by the Sharp & Dohme (S&D) Company of Baltimore. In April 1953, Sharp & Dohme merged with MSD & Company, Inc., becoming MSD Sharp & Dohme.
MSD Vaccine- More than A Century of Commitment
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Dr. Harald Zur Hausen2008 Nobel Prize (Physiology or Medicine)
Discovered the role of Human papillomavirus in cervical neoplasia.
• >190 types identified
• ≥30–40 anogenital- ~15–20 oncogenic*,
- HPV 16 and HPV 18 types account for the majority of all cervical cancers.
- Non-oncogenic** types- HPV 6 and 11 are responsible for >90% of
genital warts.
Human Papillomavirus
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90+%
~40%
~100%
60-90%
90+%
HPV
Cervical Cancer
Vulvar Cancer
Vaginal Cancer
Anal Cancer
12-70%Head & Neck
Cancer
45%Penile
Cancer
Genital Warts
Other Possible Disease burden
RRP
Preterm birth?
PROM?
Preeclampsia?
Male infertility?
Esophageal can-cer?
* RRP: Recurrent Respiratory Papillomatosis* PROM: Premature rupture of membranes
HPV Related disease
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Lee EH et al., J Korean Med Sci 2012; 27: 1091-1097
Of the 60,775 Korean women aged between 18 and 79 yr,
• Overall HPV positive rate of total patients was 34.2%.
• Age-specific HPV infection prevalence peaked at 49.9% in 18-29 year olds.
HPV Prevalence in Korea
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• 3,299 new cervical cancers are diagnosed annually in Korea.- Crude incidence rate: 13.5/100,000 women per year. - Cervical cancer is the 4th most common female cancer in women
aged 15 to 44 years in Korea.
Morbidity
WHO/ICO, Human papillomavirus and related disease report, Korea, republic of, version posted on www.hpvcentre.net in Mar 20th, 2015.
Mortality
Epidemiology of Cervical Cancer in Korea
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• 1,113 new cervical cancer deaths occur annually in Korea.- Crude Mortality Rate: 4.6/100,000 women per year- Cervical cancer is the 3rd leading cause of cancer deaths in women
aged 15 to 44 years in Korea.
Gardasil,The first vaccine to prevent cancer
• First vaccine, approved in the US on June 8, 2006 by FDA
• Contains the VLP (Virus-like Particles) of the recombinant major capsid (L1) protein of HPV types 6, 11, 16 and 18.
• Indicated for prevention of HPV 6, 11, 16, 18-related cervical, vulvar, vaginal and anal cancer & precancerous lesions and genital warts.
Introduction of HPV Vaccine
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L1 VLPs Mimic the HPV Virion(Type-Specific)
Viral DNA
Infectious HPVNoninfectious HPV VLP
Capsid proteins:L1
L2
Lacks viral DNA
LacksL2 protein
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3
North America:
USACanada Mexico
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South America:Brazil Bolivia+Argentina UruguayPeru EcuadorColombia ChileParaguay
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Middle East & Africa:
Gabon NamibiaIsrael C.A.R.+Morocco MauritiusKenya+ KuwaitMauritania UAE Guinea Eq. Ethiopia+Uganda+ Togo+Malawi+ Congo Brazzaville Congo Kinsh (DRC)+Jordan Egypt Niger+Cote d’Ivoire+ Burkina Faso+ Ghana+Chad+ Bahrain BotswanaLebanon Tanzania+ Zambia+
South Africa Cameroon+ Nigeria+Tunisia Mali+ QatarGuinea Conakry+ Saudi Arabia Rwanda+
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Asia Pacific & Japan:Kyrgyzstan+Uzbekistan+KazakhstanAustraliaIndonesia KoreaTaiwanHong KongSingaporeNew ZealandMacauMalaysiaPhilippinesThailandIndia+Vietnam+FijiBhutanJapanSri LankaBruneiAzerbaijanPakistan+TurkmenistanBangladeshCambodia
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Europe:
Germany Cyprus Ireland France Czech Republic
LatviaUK Denmark LithuaniaSpain Estonia LuxembourgItaly Finland MaltaAustria Greece NetherlandsBelgium Hungary NorwayBulgaria Iceland PolandPortugal Romania SlovakiaSlovenia Sweden SerbiaMontenegro Switzerland LiechtensteinBosnia/Herzegovina+ RussiaBelarus Croatia Turkey UkraineMacedonia AlbaniaGeorgia Kosovo
Caribbean & Central America:
Costa Rica Trinidad/TobagoPuerto Rico El SalvadorGuatemala HondurasCuracao Nicaragua+Bermuda PanamaBahamas Cayman IslandsBarbados ArubaJamaica Dominican Republic
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Gardasil / Silgard ApprovalsGARDASIL approved in 135 countries (includes 29 GAVI-eligible)
+GAVI – Eligible Registration Approvals (28 out of 56): Bolivia, Bosnia/Herze-govina, Burkina Faso, Cameroon, Central African Republic, Chad, Congo (DR), Cote d’Ivoire, Ethiopia, Ghana, Guinea (Conakry), India, Kenya, Kyrgyzstan, Malawi, Mali, Mauritania, Nicaragua, Niger, Nigeria, Pakistan, Rwanda, Tanzania, Togo, Uganda, Uzbekistan, Vietnam, Zambia, Bangladesh, Cambodia
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HPV Recommendations by National Expert Advi-sory Bodies on Immunization
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Cayman Is.
3North America
USA**Canada* Mexico
9South AmericaArgentina PeruGuyanaColombiaUruguayParaguaySurinamBrazilChile
9Middle East & AfricaKuwaitUAELesothoKazakhstanLibyaIsraelRwanda***South AfricaSeychelles
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Asia PacificAustralia**New Zealand*MalaysiaBruneiIndiaSingaporeJapanMacau
26EuropeAustria**BelgiumBulgariaCzech RepublicDenmarkFinlandFranceGermanyGreeceIcelandIreland*ItalyLatviaLuxemburgMacedoniaNetherlandsNorwayPortugalRomaniaSloveniaSpainSwedenSwitzerlandLiechtensteinUnited KingdomHungary
Caribbean & Central AmericaPuerto Rico PanamaBarbadosBermuda Trinidad & Tobago Cayman IslandsSt Martin (COM – part of EU)
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FUNDING
GARDASIL only
Bivalent Only
Both vaccines
No funding*Male Recommendation**Male Reco & Funding
***Through GAVI****will switch to Gardasil in 2014
GAVI Demo ProjectsGhana, Kenya, Laos, Madagascar, Malawi, Mozambique, Niger, Sierra Leone, Tanzania, Zimbabwe
For Female: 62 Countries – For Males: 6 countriesNational Funding: For Females: 60 Countries – For
Males: 3 countries
Population impact of HPV vaccination- Reduction in Genital warts
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HPV vaccination program introduced
Proportion of Genital warts diagnosis in Australia (< 21 years old)
Chow PF et al, Sex Transm Infect. 2015 May;91(3):214-9
• The largest decline in genital warts occurred from the 2007/2008 to the 2008/2009 periods in women aged <21 years, with a fall from 20.6% to 6.6%.
• Significant reductions in genital warts in men aged <21 years occurred from 2007/2008 (25.5%) to 2008/2009 (13.7%) to 2009/2010 (2.2%).
Population impact of HPV vaccination-Reduction in cervical lesions
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HPV vaccination program introduced
Impact on Cervical Abnormalities in Australia
JM Brotherton et al, Cancer Causes Control. 2015 Jun;26(6):953-4
• In women aged <20 years, rates have fallen from 10.9 per 1,000 screened women in 2006 (the year prior to vaccination) to 5.0 in 2013 (p<0.0001)
• In women aged 20-24 years, rates have fallen from 21.5 per 1,000 screened women in 2008 to 13.5 in 2013 (p<0.0001)
Atypia or worse CIN 2/3 CIN 30
0.10.20.30.40.50.60.70.80.9
1
1989–1990
1991–1992
1993–1994
1995–1996
1997–1999
Ha
zard
ra
tio
Population impact of HPV vaccination-Reduction in Cervical lesions
Risk for cervical lesions among vaccinated women vs. non-vaccinated women, October 2006–March 2012a,b
CIN=cervical intraepithelial neoplasia; qHPV=quadrivalent human papillomavirus.
1. Baldur-Felskov et al. J Natl Cancer Inst. 2014. doi:10.1093/jnci/djt460.
c
P<0.001 P=0.005
d
Birth cohortP=0.01
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Impact on Cervical lesions in Denmark
~80% Reduction
• Risk of atypia or worse and of CIN2/3 were statistically significantly reduced among vacci-nated women in birth cohorts 1991 to 1994.
Relative Contribution of the 7 and 2 HPV types to HPV-positive cervical cancer and precancerous cervical lesions
Next Generation HPV vaccine- 9-valent HPV vaccine
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Approved by US FDA (Dec 2014)for the prevention of
• Cervical, vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58
• Genital Warts caused by HPV types 6 and 11.
Phase III Clinical Study Results
• Appears to be safe and effective in preventing persistent infection and precancerous lesions as well as genital warts related to HPV types 6/11/16/18/31/33/45/52/58.
Next Generation HPV vaccine- 9-valent HPV vaccine
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• Ebola virus disease first appeared in 1976
• The most largest and complex outbreak in March 2014
• Ebola virus is transmitted to people from wild animals and spreads through human-to-human transmission
• The average fatality rate is around 50% and fatality rates have varied from 25% to 90% in past outbreaks
Total 26,979 cases,
Total 11125 deaths as of May 2015
How is the Ebola virus transmitted?
Introduction of Ebola Virus
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6. Household bleach and other disinfectants kill Ebola
7. Your family members, cowork-ers, and neighbors returning from countries with Ebola out-breaks don’t pose a danger to you and your family
8. Mosquitoes are the deadliest insects in the world, but they don’t carry Ebola
9. Food and drinks imported into the United States from West Africa are safe to eat and drink
10. Your dog or cat is not spreading Ebola
1. You can’t get Ebola from a handshake or a hug
2. Ebola is only spread from one person to another after symptoms begin
3. The Ebola outbreak is not affecting the safety of air-line travel
4. Ebola is not airborne5. If you’re feeling sick, think
flu not Ebola
CDC campaign: Top 10 Things- You REALLY Need to Know about EBOLA
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Cases of Ebola Virus Disease in Africa, 1976-2015
The total reported suspected, probable, and con-firmed cases in Guinea, Liberia, and Sierra Leone provided in WHO situation reports beginning on March 25, 2014 through the most recent situation report on May 27, 2015.
Ebola Virus Disease Distribution Map
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• Supportive care-rehydration with oral or intravenous fluids-and treatment of specific symptoms, improves survival
• There is as yet no proven treatment for Ebola virus dis-ease
• No licensed vaccines are available yet, but 2 potential candidates are undergoing evaluation
• Risk reduction messaging should focus on several factors:– Reducing the risk of wildlife-to-human transmission– Reducing the risk of human-to-human transmission– Reducing the risk of possible sexual transmission– Outbreak containment measure
Prevention and Control
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• Ebola vaccine candidate, rVSV-ZEBOV-GP (V920), is now included in three large-scale clinical trials in West Africa including Sierra Leone
‒ Phase II/ III safety and effectiveness study, called STRIVE (Sierra Leone Trial to Intro-duce a Vaccine against Ebola), taking place in Sierra Leone Will involve 6,000 health and other frontline workers
‒ The Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) which is Led by a Liberia-U.S. clinical research partnership and sponsored by NIAID
‒ Designed to enroll approximately 27,000 healthy men and women aged 18yrs and older
“Fighting Ebola remains a global health priority, and MSD is committed to advancing the development of our and NewLink’s vaccine candidate as part of our overall response to the crisis”
‒ Mark Feinberg, M.D., Ph.D., chief public health and science officer
R&D on Ebola Virus
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(- Much greater value in a context of new disease conquests- Reiterate beneficial effect of vaccine with the example)
IFPMA. Vaccines for Prevention. Available at http://www.ifpma.org/fileadmin/content/Resources/Vaccines/Vaccine_Pipeline_Chart.pdf accessed on Jun 1st 2015
Vaccines in development
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HPV-related cancers, HPV Vaccine (9 valent) (V503) is an investigational human papillomavirus (HPV) vaccine that targets nine HPV subtypes: 6, 11, 16, 18, 31, 33, 45, 52 and 58. V503 is being evaluated for prevention of HPV
V212 is an investigational, inactivated varicella zoster virus (VZV) vaccine candidate. It is being evaluated for the prevention of herpes zoster (HZ) and HZ-related complications in select immuno-compromised patient populations.
Data on file, MSD
MSD Vaccine pipelines
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