Upload
jocelin-wade
View
213
Download
0
Tags:
Embed Size (px)
Citation preview
New developments in HPV vaccines
Ian Frazer, Research Director, The Translational Research Institute Brisbane, Australia
Cervical cancer is 100% due to HPV infection, and kills 250,000 women per year, mostly in the developing
world
ALL CANCERS CERVICAL CANCER
Papillomavirus vaccine development
Cancer associated Human
Papillomaviruses(~1980)
Zur Hausen
Harriet Richardson, Gail Kelsall, Pierre Tellier, Helene Voyer, Michal Abrahamowicz, Alex Ferenczy, Francois Coutlee, and Eduardo L. Franco Cancer Epidemiology, Biomarkers & Prevention Vol. 12, 485–490, June 2003
HPV 16
First learn the natural history of the disease
Fract
ion infe
cted
Months since onset of Sexual activity- High risk HPV infection is common- Two common (16,18) and several rarer
types- >95% resolve spontaneously –median
1.5yrs- 2% progress to cancer over 15 years- Unexpectedly, detection of pre-cancer is
possible 1- 2 years post infectionR
esi
dual in
fect
ion
Vaccines to prevent HPV infection
Cancer associated Human
Papillomaviruses(~1980)
-Some HPVs cause cancer - Virus can’t be grown in the lab
Virus Like particles1
(~1990)
- L1 recombinant DNA
- Self assembly to VLPs
- VLPs highly immunogenic
1:J. Zhou, X. Y. Sun, D. J. Stenzel, and I. H. Frazer. Virology 185 (1):251-257, 1991.
Jian Zhou
Zur Hausen
HPV vaccine development:A 15 year $1 billion process
Cancer associated
Human Papillomaviruses
(~1980)
Virus Like particles1
(~1990)
HPV vaccines(~2005)
-Conventional vaccines- VLPs+ adjuvant
- Neutralising Antibody- Protection > 5yrs
-Cervarix – HPV 16, 18-Gardasil – HPV 6,11,16,181:J. Zhou, X. Y. Sun, D. J. Stenzel, and I. H. Frazer. Virology 185 (1):251-257, 1991.
Jian Zhou
Zur Hausen
Disclosure of conflict of interest
Dr Ian Frazer and the University of Queensland benefit financially from commercial sale of the prophylactic HPV vaccines discussed in this talk
-needing many people and a hard end point to prove efficacy
Study1 Vaccine2 No of subjects End-points
Vaccine efficacy1
Vaccine Control % ( confidence limits)
Koutsky 6/11/16/18 6087 6080 CIN 2/3 AIS 98 (86-100)
Ault 6/11/16/18 10291 10292 CIN 2/3 AIS 99 (93-100)
Garland 6/11/16/1822412261
22582279
CIN 2/3 AISGW VIN VAIN
100 (94-100)100 (94-100)
Joura 6/11/16/187811 7785 VIN2/3 VAIN
2/3100 (72-100)
Parvonen* 16/18 9319 9325 CIN2,3 93 (89-98)
Adapted from J. A. Kahn and R. D. Burk. Papillomavirus vaccines in perspective. Lancet 369 (9580):2135-2137, 2007.
*: Phase III bivalent vaccine data from 25th IPV Malmo 2009
1: prevention of premalignancy in HPV naïve subjects, for prevention of disease caused by vaccine HPV types
Since the introduction of vaccination in Australia,HPV related disease has virtually disappeared in
vaccinated young women
Ali, H. Et al BMJ 2013;346:f2032 doi: 10.1136/bmj.f2032
Nine steps to prevention of HPV associated cancer
• Define the problem – HPV and cancer Zur Hausen
• Develop the science –recombinant VLPS Jian Zhou• Find commercial partners
Merck/GSK• Scale up the manufacture
Merck/GSK• Complete safety and efficacy trials Many
groups• Educate the profession, govt, the public Ongoing• Confirm field efficacy • Improve the product
– 9 valent vaccines, 2 dose regimens• Encourage deployment globally• Develop effective immunotherapy
3
North America:
USACanada Mexico
9
South America:Brazil Bolivia+Argentina UruguayPeru EcuadorColombia ChileParaguay
38
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+
25
Asia Pacific & Japan:Kyrgyzstan+Uzbekistan+KazakhstanAustraliaIndonesia KoreaTaiwanHong KongSingaporeNew ZealandMacauMalaysiaPhilippinesThailandIndia+Vietnam+FijiBhutanJapanSri LankaBruneiAzerbaijanPakistan+TurkmenistanNepal
42
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
Caribbean & Central America:
Costa Rica Trinidad/TobagoPuerto Rico El SalvadorGuatemala HondurasCuracao Nicaragua+Bermuda PanamaBahamas Cayman IslandsBarbados ArubaJamaica Dominican Republic
16
HPV Vaccine Approval is world-wide
+GAVI – Eligible Registration Approvals (27 out of 56): Bolivia, Bosnia/Herzegovina, 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, Nepal.
HPV vaccine use (in green) is in the developed world
Cervical cancer (in purple) is in the developing world
http://www.indexmundi.com/blog/wp-content/uploads/2013/05/HPV-vaccine-infographic.jpg
Study 1 -Screening
• Aim: Compare cervical cancer screening strategies in 30 + year old women
• P.I. : Dr Mgt McAdam• Methods:
– 500 women between 30 and 50 recruited
– VIA, VILI, Colposcopy, Cervical Cytology (Brisbane), HPV DNA (Digene)
– Referred for biopsy if any test positive.
1% of Vanuatu women will get cervical cancer! Vaccine delivery needs staffing, and a cold chain
Vanuatu->50 islands~250,000 people~25 doctors-91 parliamentarians!-1 vaccine fridge-0 reliable electricity
500 well women over 30
Bx result Number
Cancer 5
CIN 3 17
CIN 1 23
Education is the key to successful vaccine delivery: parents, children, staff, and government
Parents and Kids under the Banyan Tree- north Efate
16
When vaccine is available, vaccination programs can be as
successful in Vanuatu as Australia
State Age Dose 1 Coverage (%)
Dose 1 immunised receiving
Dose 2 (%) Dose 3 (%)
Australia 12-18 (Opt out)
~ 90% 96 86
Australia 18-25 (Opt in) ~80% 82 50
Vanuatu 10-12 (Opt out)
~80% 98 93~80% coverage for bivalent HPV vaccine for 10-12 year olds in 2008, and 2013Vaccine through Australian Cervical Cancer Foundation: delivery by government
cUNICEF Australia Cyclone Pam appeal
Red Cross Cyclone Pam Appeal
Oxfam Australia International Crisis Fund - Cyclone Pam
CARE Australia Cyclone Pam Response or call 1800 020 046
Save The Children Cyclone Pam Appeal or call 1800 76 00 11.
Emergency appeals that you can donate online to for Nepal include:
Oxfam Australia
Medecins Sans Frontieres
(Doctors Without Borders)
CARE Australia
World Education Australia
UNICEF Australia
World Vision Australia