Title: Vaccine development in Russia: current situation and prospects Prof' I'V' Krasilnikov
1Vaccine development in Russia current situation
and prospects Prof. I.V. Krasilnikov
2- Mass immunization allows to
- decrease the child death rate
- lengthen live expectancy
- raise quality of life
- decrease the risk of invalidization and loss of
work capacity.
3- Vision a world in 2015 in which
- immunization is highly valued
- every child, adolescent and adult has equal
access to immunization as provided for in their
national schedule - more people are protected against more diseases
- immunization and related interventions are
sustained in conditions of diverse social values,
changing demographics and economies, and evolving
diseases - immunization is seen as crucial for the wider
strengthening of health systems and a major
element of efforts to attain the Millennium
Development Goals - vaccines are put to best use in improving health
and security globally and - solidarity among the global community guarantees
equitable access for all people to the vaccines
they need.
Global Immunization Vision and Strategy (GIVS)
for 2006-2015 (Adopted at the fifty-eighth World
Health Assembly, 28.04.2005)
4National immunization programmes
5Vaccine production and RD priorities for
Russian biopharmaceutical industry
- To develop and launch for public use
- a Hib Vaccine
- a Hepatitis C Vaccine
- an AIDS Vaccine
- a Human Papilloma Vaccine.
- To create new antigen delivery systems and
vaccines in different forms (nasal spray,
emulsions and etc.). - To develop new combined vaccines, gene
engineering vaccines and therapeutic vaccines.
6WHO Global Pandemic Influenza Action Plan to
Increase Vaccine Supply (GAP)
-
- Objective To increase the supply of a pandemic
vaccine and thereby reduce the gap between the
potential vaccine demand and supply anticipated
during an influenza pandemic (November 2006) - Increase in seasonal vaccine use
- Increased use of seasonal influenza vaccine
will reduce disease burden of seasonal influenza
infections, contribute towards the preparedness
of countries to respond to an eventual pandemic
and motivate industry to develop greater capacity
for manufacturing vaccines. - Increase in vaccine production capacity
- Short term Produce enough vaccine to
immunize two billion people this vaccine should
be available on the market six months after
transfer of the vaccine prototype strain to
industry. - Medium and long term Produce enough
vaccine to immunize the world's population (6.7
billion) - Further research and development
- The development of more effective influenza
vaccines using new technologies.
7WHO Global Pandemic Influenza Action Plan to
Increase Vaccine Supply (GAP)
The ideal product profile is a vaccine which is
safe and highly protective, preferably in all
target groups, including infants, the elderly,
pregnant women and immunosuppressed
individuals is easily and inexpensively
produced on a large scale is effective
preferably with a low dose of antigen is
delivered, ideally, as a single dose, is
thermostable and offers protection for a
minimum duration of one year, including
protection against antigenically drifted viruses.
8Vaccine for Humans against the Avian Influenza
Virus H5N1 has been successfully developed in RF
- Three pre-pandemic vaccine candidates based
on the H5N1 avian influenza virus strain NIBRG-14
(A/VietNam/1194/ 2004/A/PR8) received from NIBSC
and the H5N2 avian influenza virus strain
A/17/Duck/Potsdam/86/92 Len17/H5 developed by
the Russian scientists were designed in the
company production sites in Ufa and Irkutsk. They
are - Inactivated subunit adjuvanted with aluminum
hydroxide - Inactivated split adjuvanted with aluminum
hydroxide - Live attenuated influenza vaccine (LAIV)
stabilized with M-2
9Clinical studies of prepandemic vaccines
- H5N1 inactivated prepandemic vaccines
- Clinical base Research Institute of
Influenza RAMS in St. Petersburg and Mechnikov
Research Institute of Vaccines and Sera in
Moscow. - Dose, Volume, Route 2 intramuscular doses
of the vaccine with 15, 30 and 45 µg of HA in 0.5
ml, administrated 28 days apart. - The number of participants about 600
healthy adults. - H5N2 LAIV candidate (6,9 and 7,5 lg EID50/0,5
ml) - Clinical base Clinic 163 of the Federal
Medicobiological Agency of Russia (Novosibirsk
region) and Military Hospital 1137 (Moscow
region) - Dose, Volume Route 2 intranasal doses
sprayed 0,25 ml into each nasal track (0,5 ml
dose) - with a 10 and 21 days intervals.
- The number of participants 220 healthy
adults. -
- Pre-clinical and clinical trials
demonstrated safety, areactogenicity and high
immunogenicity of all pre-pandemic vaccine
candidates. They have induced a strong protection
against the homologous vaccine strains and the
other heterologous H5N1 HPAIV strains including
the Russian epidemic isolate A/Chicken/Kurgan/Russ
ia/2/2005 (H5N1).
10- OrniFlu, an inactivated subunit influenza
vaccine, and Ultragrivak, a live influenza
vaccine, are licensed in the Russian Federation. - Microgen State Scientific Industrial Company is
ready to start a large-scale production of avian
influenza vaccines for humans in the amount that
will allow to provide the Russian population with
the vaccine in full. -
11Did I tell you - there will be no avian influenza
!
12H1N1v influenza vaccines
- Microgen has designed two pandemic vaccines,
- an inactivated subunit and LAIV, against new
H1N1v influenza strain on the base of our
previously developed pre-pandemic avian flue
vaccines. - The clinical evaluation of these candidate
vaccines has been started in September and mass
production is planned to be launched in November
2009.
13DEVELOPMENT OF AN ACELLULAR PERTUSSIS VACCINE
- An acellular pertussis vaccine developed in
Microgen Scientific Industrual Company is less
likely to provoke adverse events compared to a
whole-cell pertussis vaccine because it contains
purified antigenic components of Bordetella
pertussis. In terms of immunogenicity it
possesses the same capacity to confer protection
upon humans. The acellular vaccine demonstrated - a 3-fold decrease in acute toxicity LD50,
- a 100-fold decrease in anaphylactogenicity,
- a 120-fold decrease in pyrogenicity,
- a 9-fold decrease in HSD50,
- a 19-fold decrease in leucocytosis.
- Pre-clinical evaluation of the vaccine candidate
has proved its safety, high histamine-sensitizing
activity and protective potency.
14DEVELOPMENT OF A NEW CLASS OF VACCINES THAT
ACTIVATE INNATE IMMUNITY
- A polybacterial vaccine Immunovac VP-4 composed
of S.Aureus, E.Coli, K.Pneumonia, P.Vulgaris
antigen complexes has been created in close
collaboration with I. Mechnikov Research
Institute for Vaccines and Sera, RAMS. - The clinical studies of the vaccine have shown
its high efficacy, safety, good tolerability and
prolonged and potent therapeutic and prophylactic
effect. High immunogenicity of the vaccine
preparation can be explained by the phenomenon of
cross-immunity while safety is obtained by the
decrease of antigenic load. The polybacterial
vaccine exerts a positive effect on different
diseases - - bronchial asthma 71
- - chronic bronchitis 95
- - lung abscess 75
- - herpes 90
15DEVELOPMENT OF A NEW CLASS OF VACCINES THAT
ACTIVATE INNATE IMMUNITY
- Immunoprophylactics with Immunovac VP-4 allows to
indicate - - 11 time relapse rate reduction in sickly and
chronic children during 7 months, - - 3 time acute respiratory disease rate decrease
in sickly and chronic children during 12 months, - - 6 time allergy disease severity (in scores)
decrease, - - 50 or more tumor size reduction in oncological
processes.
16DEVELOPMENT OF A RUBELLA VACCINE
- In 2007-2008 cell culture-based rubella
vaccine technology in MRC-5 (Stanley A. Plotkin)
was developed. The production strains, the seed
strains and all the intermediate passages of
rubella virus strains have been obtained. The
control tests to determine their biological
sterility, specific activity, physico-chemical
properties and the absence of mycoplasma have
been performed. The vaccine candidate has
entered Phase I clinical trials. -
- The benefits
- - there is no analogues produced in Russia,
- - simple and cost-efficient vaccine
production technology in MRC-5 human diploid-cell
culture allows rubella virus to be grown at high
concentrations, - - the series of the vaccine candidate for
children are sorbitol based, there is no nutrient
medium added, which allows to decrease ballast
protein concentration.
17Thank you for attention