Jeffrey Almond

25 Pages·2009·0.75 MB·English

Karl Landsteiner
Poliovirus vaccines: Their
development and use, now
and in the future
Jeffrey Almond
Vice PresidentDiscoveryResearch
and ExternalR&D
sanofi pasteur
Outline
Briefly revisit OPV and IPV history
Summarize the OPV experience and progress on global
eradication
Summarize IPV experience and recent developments
Conclude on future requirements and options available
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Significant progress to control polio made over the past 20
years thanks to the Global Polio Eradication Initiative
Polio Eradication Progress, 1988-2008
1988 / 350,000 cases estimated 2008 / 1,655 cases
Certified Polio-free regions (114 countries)
Not Certified but non-endemic (73 countries)
Endemic with wild polio virus (4 Countries)
TThhaannkkss t oto G GPPEEI,I ,> >55 m mililliloionn p peeoopplele h heeaaltlhthyy t otoddaayy, ,w whhoo w woouuldld h haavvee b beeeenn
ppaarraalylyzzeedd, ,h haadd t htheeyy n noot tr reecceeiviveedd p pooliloio v vaaccccinineess
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Adapted from WHO GPEI communication
Despite sustained investment, Global Polio Eradication
Initiative is facing significant challenges
Global Polio case count [2000-2009*] GPEI Annual Expenditure [1988-2008]
*As of October 20th Financial Resource Requirements, Contributions
and Funding Gap 2009 -2013
2971
3000
2500
1922 1951 1996
2000
1655
1500 1258 1308 1198*
1000 784
498
500
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
>>11,5,50000 c caasseess/y/yeeaarr r reeppoorrtetedd s sininccee 2 2000055 l eleaaddiningg t oto i tieterraatitvivee G GPPEEI It itmimeelilnineess s shhifitft
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Adapted from WHO GPEI communication
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Polio is still endemic in 4 countries, reflecting both
“vaccination failure” and “failure to vaccinate”
West UP Bihar Rest of country
Polio Endemic countries in 2009 100%
80%
Polio cases despite high vaccination coverage (cid:198)
60% Vaccine Failure (Poor OPV efficacy)
INDIA
40%
20%
0%
2003200420052006 20072008 2003 2004200520062007 2008 20032004 2005200620072008
0 dose 1-3 doses 4-6 doses 7+ doses
High risk Medium risk Rest of country
100%
80%
NIGERIA
60% Failure to vaccinate
WWhhiliele a awwaarreenneessss/p/prrooggrraamm a assppeecctsts a anndd 40%
ppooliltiitcicaal lb buuyy-i-nin a arree a at ts statakkee i nin A AFFGG, ,P PAAKK a anndd 20%
NNIGIG, ,i mimmmuunnizizaatitoionn s strtraateteggieiess c coouuldld b bee
rreevvisisitietedd i nin I nInddiaia 0%2003 2004 2005 2006 2007 2008 2003 2004 2005 2006 2007 2008 2003 2004 2005 2006 2007 2008
0 dose 1-3 doses 4-6 doses 7+ doses
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Adapted from WHO GPEI communication
The Early days
Of Polio
Vaccines
Egyptian stele (stone carving) dating bet. 1580 and 1350 B.C
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Poliovirus
.
Poliovirus was discovered by Karl Landsteiner in 1909
In collaboration with C. Levaditiof InstitutPasteur Paris, the infectious agent
was shown to be a filterable virus that could spread along nerves and be
transferred between monkeys
John F. Enders and his coworkers (Weller and Robbins) discoveredin 1949 a
method of growing the viruses on tissue in the laboratory
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Jonas
Salk
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1st Salk Polio Vaccine
1/ Salk, Jonas & al., Federation Proc. 11:480, 1952 Immunizationof
Monkeys with Polioviruses grown in Cultures of Monkey Tissue
2/ Salk, Jonas & al., J.A.M.A., March 28, 1953 Studies in Human Subjects
on Active Immunization Against Poliomyelitis
Type 1 :Mahoney
Type 2 :MEF-1
Type 3 : Saukett
Inactivation : 0.4% of a 37% solution of formaldehyde USP. Test of inactivation in
cynomologusmonkeys by intracerebralinoculation of 0.5ml of fluid in 6 to 10
animal.
National Foundation places a $9 million order to six drug companies to start
stockpiling.
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The Francis Field Trial
A total of 1,829,916 children in communities from all parts of the US, Canada
and Finland participated. The experiment involved vaccinees, observed
controls and placebo controls.
On April 12, 1955, Jonas Salk, along with his mentor,
Dr. Thomas Francis, and the March of Dimes announced :
The Salk polio vaccine works.
"Safe, effective, and potent." The Salk polio vaccine
was 60-90% effective in preventing paralytic polio.
On the basis of the results of the trial and the data presented by 6
manufacturers, the Salk Vaccine was licensed within a few days after these
results were announced.
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Albert
Sabin
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Sabin live attenuated Oral Poliovirus Vaccine
(OPV)
Hilary Koprowskihad started work on an attenuated oral vaccine in 1948
at Lederle. First clinical trials were in 1950. A mass immunization
campaign was organized in the Congo in 1957 with a type 1 vaccine, and
soon a type 3. By 1959 over 46,000 children had been immunized with the
type 1. Efficacy in that tropical setting was 60%.
Sabin started working on attenuated strains in 1953. Merck Laboratories
prepared industrial lots of genetically segregated strains in 1956. Sabin
convinced the Russians to try the vaccine in the Soviet Union.
In 1957 the World Health Organization (WHO) decided Dr. Sabin's vaccine
deserved world-wide testing. He was invited to administer the vaccine to
large groups of children in parts of Russia, Holland, Mexico, Chile,
Sweden, and Japan.
1961/2 monovalentoral poliovirus vaccines (MOPV) licensed; 1962.
1963, trivalent oral poliovirus vaccine (OPV) licensed.
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Effects of vaccination against Poliomyelitis
USA
Poliomyelitis in the USA. 1951-1978 [reproduced from
Salk, D. Rev. Infect. Dis. 1980 2, 228 by permission of the University
Of Chicago Press]
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Significant progress to control polio made over the past 20
years thanks to the Global Polio Eradication Initiative
Polio Eradication Progress, 1988-2008
1988 / 350,000 cases estimated 2008 / 1,655 cases
Certified Polio-free regions (114 countries)
Not Certified but non-endemic (73 countries)
Endemic with wild polio virus (4 Countries)
TThhaannkkss t oto G GPPEEI,I ,> >55 m mililliloionn p peeoopplele h heeaaltlhthyy t otoddaayy, ,w whhoo w woouuldld h haavvee b beeeenn
ppaarraalylyzzeedd, ,h haadd t htheeyy n noot tr reecceeiviveedd p pooliloio v vaaccccinineess
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Adapted from WHO GPEI communication
VAPP
(Vaccine associated paralytic
poliomyelitis)
VDPV
(Vaccine-derived Polio viruses)
and
Long term excretors
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Table 1 Base atposition 472, time of isolation, neurovirulenceand
temperature
Sensitivityof Sabin type 3 vaccine-derivedstrainsof poliovirus
Virus Base at Time of Mean Rct
position 472 isolation after histological marker
vaccination lesionscore test
Sabin
U 0.36 > 5.5 (rct-)
vaccine
DM1 U 24 H ND ND
DM2 U 31 H 1.58 6.13 (rct-)
DM3 U / C 35 H ND ND
DM4 C 47 H 2.48 5.71 (rct-)
DM38 C 18 days ND ND
DM119 C 3-4 weeks 3.34 0.25 (rct-)
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