Symposium on Development of Vaccines for Viral Infections
(December 12-14, 1994)
Koltsovo, Novosibirsk region, Kussia

Introduction:

A symposium on development of vaccines for viral intections was held on
December 12-14, 1994 at the State Research Center of Virology and
Biotechnology "VECTOR." ‘Lhe meeting was organized by the International
Science and Technology Center (ISTC) with the help of VECTOR. The main
purpose of the symposium was to bring together Russian and foreign experts
in focussed areas of viral vaccine development in order to improve VECTOR
proposals and planned projects to the ISTC. The agenda for the scientific
program is attached (Attachment 1). Forcign participants included eight
experts from the European Union and three delegates from the United States.
Japanese experts were also invited but were unable to attend. ‘Ihe list of
delegates, including 6 Russian experts invited from Moscow, is attached
(Attachment 2). A large number of VECTOR personne! were also involved
in the symposium via presentations, discussions, and tours of VECTOR
facilities.

December 12, 1994:

The first day of the symposium featured a plenary session composed of more
general presentations on the central topics of the sympusium. Academician
Sandakhchiev, General Director of VECTOR, opened the symposium with a
welcome to the participants. A copy of his remarks is attached (Attachment
3). Professor Kasella, the current Chairman of the ISTC Governing Board,
followed with presentation on the status of the ISTC. He noted that 93
projects, costing more than $47 million, have been approved for scientific
projects in the Russian T'ederation and Georgia. Hc stated that projects
involving vaccine development and other medical and health conversion
topics have a high priority.
The technical presentations began with a talk by Dr. Vinogradova, Head of
Department of the State Committee of Epdemiological Surveillance of the
Russian Federation. She discussed the past and current state of health in the
Russian Federation with respect to viral infections. She noted that carlicr
successes took place in reducing polio and measles, but that the current poor
economy has led to a general increase in viral infections throughout the
Russian Federation. She noted the current serious level of Hepalilis A and B
infection and attendant health threats to the population, especially to children.
The need for increased vaccination was described (see Attachment 4).

A talk on the side effects and immunological safety of vaccines was
presented by Professor Medunitsin, Director of the Institute of
Standardization and Control of Medicinal Immunological Preparations
(RGIST). He reviewed the possible side effects of using vaccines and
discussed the safety measures taken to reduce the chances of these effects
(see Altachment 5). The Russian Federation requirements for oblaining high
quality vaccines were presented by Professor Bektimirov, Deputy Director of
RGIST. He pointed out that RGIST acts like the FDA in the US to inspect
batches of vaccine and manufacturing facilities. Lhe contro! process used in
the Russian Federation for development and production of vaccines 1s
discussed in his attached paper (see Attachment 6)-

‘The regulations for immunological medicines in the European Union were
presented by Dr. Pletshettc, Commission of the European Communities, and
Dr. Jepsen from the Office of International Health of Denmark. They

brought a full copy of these regulations to the symposium and gave them to
VECTOR. The regulations include those related to safely, testing quality,
and marketing. ‘hey discussed the quality assurance program used in the EU
countries that focusses on good manufacturing practices combined with
quality control. They advised the Russian producers of vaccines to start with
lower cost training and general upgrade of personnel to be followed by
renovation of facilities.
Dr. Rick Smith, from Connaught Laboratories in the US, reviewed the good
manufacturing practices advocated by the FDA in the US. He discussed the
need to constantly improve under the LIS practice, hased on the fact that a
new idea quickly becomes the new standard. He said that the FDA inspects
each laboratory at least every two years.

The final presentation of the plenary session was given by Academician
Sandakhchiev. He discussed the topic of conversion of VECTOR to peaceful
technologies from their former involvement in defense activitics. He detailed
the diverse capabilities of VECTOR to develop and procnice vaccines against
viral infections (scc Attachment 7).

In the afternoon, visitors to VECTOR were allowed to visit several of their
facilities, including the laboratories concerned with development of vaccines
against Hepititis A and measles, a laboratory for study of HIV, the
laboratory for biological and technology control, and the area where
production of drugs and test systems is being prepared. Several people also
visited the nursery for laboratory animals.

December 13, 1994:

The second day of the symposium was devoted to detailed discussion of two
approved ISTC projects for development and production of Hepatitis A and
measles. ‘l'wo other proposals tor (1) development and production of
Hepatitis B vaccine and (2) for clinical tnals of new vaccines were also
discussed. ‘hese discussions were carried out in a workshop format. The
proposed Russian project manager gave a prepared talk followed by detailed
interchange of ideas and comments by working group participants.
Inactivated Hepatitis-A Vaccine:

A prepared talk was presented by Dr. Maidaniuk, Head of Department at
VECTOR. He discussed the virus strain, the production procedure, and
formulation and guality control of the final virus (see Attachment 8). Issues
discussed in the workshop included the cell line proposed based on the
kidney of the African green monkey. Western experts suggested that a
different cell line based on the human diploid fiberblast would give

VECTOR a better market opportunity because this is the cell line used in the
West.

The second session speaker was Dr. Vinogradova, Head of Department from
the State Committee of Epidemiological Surveillanve of the Russian
federation. She discussed the requirements and methods of control of the
quality of Hepatitis-A vaccine in Russia (Attachment 9). She noted that
VECTOR and RGIST have tested a series of vaccines against Hcpatitis-A.
The triple scheme of vaccination has been found to be optimum. The issue
of proposed vaccinations of children was raiscd. She noted that no
vaccination of children is done hefore completion of trials on adults. They
will use lesser concentrations for children.

The Western experts expressed general support for implementation of this
project, under the conditions of having collaborators from the European
Union and the US involved. It was also suggested that one or two people
from RGIST should participate actively in the work.

Live Measles Vaccine:

Dr. E. A. Nechaeva, Head of Department at VECTOR, gave a presentation on
the claboration and production of a live measles vaccine (Attachment 10).
She descrihed the vaccine strain Teningrad-16 used in Russia in the
production of the measles vaccine. She descri bed how mass vaccination
against this killer of children began in Russia in 1967. The project will
develop and produce an oral vaccine preferred for children and without the
possibility of hepatitis-B or HIV transmission through needles.
Professor Popov, Head of Department from RGIST,, discussed the situation
with respect to measles vaccine in the Russian F ederation (see Attachment
11). He mentioned that Russian measles vaccine is currently exported to
several developing countries, including Vietnam, Brazil, and Peru. Tests
have been conducted at her institute that confirm the. stahility of the hasic
vaccine strain for many ycars.

An issue raised during this session included the need to characterize the
Russian strain so thal il can be compared to strains on which other vaccines
around the world are based. Some doubts were also expressed about the
efficacy of the delivery system for the ural vaccine.

The Westem experts generally supported initiation of the project, subject to
independent and parallel analysis of the strain in an EU laboratory and tests
to determine if the strain would actively work once it reaches a receptor in
the gut. Failure to prove ot the efficacy of the oral delivery method would
seriously compromise the project, and would probably eliminate support tor
later phases of the proposed work.

Hepatitis-B Vaccine:

Dr. Muratov, a scientist at VECTOR, made a presentation on creation and
production of the recombinant vaccine against [epatitis-B (scc Attachment
12). He described the VECTOR work with the Vacinia virus. Re mentioned
that for the live vaccine, the recombinant protein is active in the antigen-
presenting cells, reliably introducing a T-cell response. He saw the proposed
project as the opportunity for them to organize a large scale production of a
inexpensive, effective, and innocuous vaccine against Hepatitis-B in an oral
form.

Dr. Shalunova, Senior Scientist at RGIS, discussed the situation with
respect iv Hepatilis-B vaccine in the Russian Federation (Attachment 13).
She also reviewed the worldwide problem of Hepatitis-B infection and the
ueed in Russia to produce low-cost, highly-effective vaccine that overcomes
public resistance to vaccination. .
Western experts raised scvcral issues: They see a problem with possible
dispersion of the live virus in the environment. They see possible exclusion
of people who received smallpox vaccinations. Some felt that it is also
difficult to judge whether there might be side effects. One recommendation
was to include the core protein in a vaccine construct suitable for vaccination.
The Russian scientists see a vaccination program as having many drawbacks
and think an oral vaccine is still preferrable.

Clinical Trials of New Vaccines:

‘Lhe possibilities of clinical trials of new vaccines at VECTOR was presented
by Dr. Netesov, Deputy Director of VECTOR. He discussed the capabilities
of the P-3 facilities at VECTOR to be used in the clinical trials of new
vaccines, in particular against diarrheal diseases, especially cholera (see
Attachment 14).

Wester experts raised issues concerned with the proposed clinical] trials and
the current adequacy of the VECTOR facility. They madc the following
recornmendations: To extend the immunological investigations, especially
concerning the T-shell immunity parameters of volunteers during and after
vacclwation. It is also uecessary to include into the list of equipment some
small equipment for measuring the cell immunity parameters and the
expenses for training of VECTOR specialists with modern methods. To
make marketing investigations for finding additional! otters for vaccine
testing. To extend the facilities for immunological work in P-3 and increase
the equipment for blood and urine analysis. To add the position of Biosafety
Control] Officer for the trials and a Bookkeeper.

December 14, 1994:

The third day of the synyposium was devoted to a talk on production of test
systems and tours of Russian Academy of Science Institutes in the area.
Dr. Zaitsev, Deputy Director of VECTOR (Attachment 15), discussed
production of test systems and research reagents for the diagnosis of viral
diseases and perspectives in their development. Additional remarks were
provided by Professor Vorobiova, Head of Department of RGISK. The
range of testing and diagnostics is very broad at VECTOR, including those
for HIV 1&2, Hepatitis A, B, C, and D, meaasles, herpes, syphilis, and many
others. VECTOR hopes to expand its production facility in 1995 and receive
a European certitication in 1996. They hope to expand their sales thereafter
in several countries.