Transcript Slide 1

BHK-21 RABIES VACCINE
– A CANDIDATE VACCINE
FOR HUMANS
Dusan Lalosevic, MD, Ph.D.*
Pasteur Institute in Novi Sad, Serbia
*Present address: Faculty of Medicine and Clinical
Center in Novi Sad, Serbia
Country Report
In the North community
Subotica, a trial of oral
vaccination started by deltaplanes sponsored by
VIRBAC
BHK-21 C 13 cell culture is well known substrate
for animal rabies vaccine production
BHK-21 C 13 cells are much
better producers of rabies
virus than HDC or VERO
cells…
Baer G.M. Improvements in Rabies Post-Exposure
Treatment, Dubrovnik, Yugoslavia, 1984, pp. 1524:
Only BHK-21 rabies
vaccine induced
interferon (in mice and
monkeys), HDC did not!
… and rabies vaccine production is
possible in local institutes…
Vaccine. 2006 Mar 20;
Immunogenicity and efficacy of an in-house developed cell-culture derived
veterinarian rabies vaccine.
Kallel H, Diouani MF, Loukil H, Trabelsi K, Snoussi MA, Majoul S, Rourou S,
Dellagi K.
Unite de Developpement de Vaccins Virologiques, Institut Pasteur, 13 Place Pasteur,
BP 74, 1002 Belvedere, Tunis, Tunisia.
The efficiency of an inactivated tissue culture rabies vaccine produced on BHK-21
cells, according to an in-house developed process, was evaluated and compared to a
commercial cell-tissue culture vaccine (Rabisin). Fifteen experimental dogs from local
common breed were duly conditioned during a quarantine period, then vaccinated via
the subcutaneous route with 1ml of either the tissue culture vaccine developed inhouse or the commercial vaccine Rabisin. The immune response of each dog was
monitored for 162 days. Serum-neutralizing antibodies titers to rabies virus were
determined by the rapid fluorescent focus inhibition test (RFFIT) which confirmed the
strong response of dogs to both vaccines except one dog in the Rabisin group...
… but up today only for animals.
If a BHK vaccine is good
for animals for many
years of experience, is
this vaccine good for
humans too?
It’s a question of the
WHO and we have the
first answer from late
professor Sureau…
Nero
Sureau P. Recent Data on Human
Immunization Agains Rabies.
Symposium on Rabies, Novi Sad,
17-19th April, 1991
At that time, professor Sureau
wrote very carefully:
Yes, we regularly induced tumor on the
inoculation site of suspension of BHK – 21
cell culture, but…
… tumor is solitary, enormous, and never produced
metastases.
Tumor cells are very similar as BHK 21 C 13 in vitro,
Summary of tumorigenicity of BHK21 C 13 cell culture
• This tumor have not the first and most important
criteria for malignancy – metastases formation!
• BHK-21 cells are tumorigenic only for hamsters
(except nude mice)!
• Only whole live cells are tumorigenic, not DNA, or
cell extracts – It’s a transplantation of cells!
• Conclusion: BHK tumor is in vivo culture of BHK-21
C 13 cells!
• Hypothesis: Immunologicaly, hamsters do not
recognize BHK-21 cells as tumorigenic! Becouse of,
transplant growing to enormously tumor masses.
DNA contamination?
• Perrin P, Morgeaux S. Inactivation of
DNA by beta-propiolactone. Biologicals
1995, 23, 207-211.
• ‘Product may be considered safe on the
basis of … the possible inactivation of any
biological activity of contaminating DNA
during processing…’ WHO TRS 878,
Geneva, 1998, p. 26.
We accepted their
opinions and
started with “enhouse” rabies
vaccine production
in Pasteur Institute
in Novi Sad, Serbia,
for human use,
named
YU BHK Rabivak.
Vaccine was attested
in the National
Center for
Epidemiology
”Johan Bela” in
Budapest, a WHO
accredited
Laboratory for
vaccine control,
under supervision of
Imre Lontai, MD,
Ph.D., Head of
Rabies Laboratory in
2001 year, and also
in…
…Russian Academy
of Medical Science
Institute named by
M.P. Chumakhov,
under supervision of
professor V.P.
Grachev, and the
result of vaccine
potency was over
2,5 IU/ml
The first lot of vaccine was
re-attested after 5 years
storage at +4 and had 2.6
IU/ml
5 th July 2006
2.6
IU/ml
Clinicaly examination on volunteers
•Research staff of Pasteur Institute
in Novi Sad (mainly are
microbiologists),
•External collaborators included an
expert in vaccine control and few
veterinarians,
•Hunters
All received:
•Three doses of vaccine in days 0,
7, 21;
•99/100 had antibody titre over 0,5
IU by RFFIT after 30 days;
•1/100 received one additional dose
and than have titre over 0,5 IU.
Petricciani J.C.
• What will happened if BHK-21 cell culture
rabies vaccine is used on humans?
• “If such vaccines, which cost as
little as 0.50 dollars per dose in
USA, could be used for human
beings, the result would be an
enormous reduction in (rabies)
morbidity…” Petricciani J.C. Ongoing
tragedy of rabies. Lancet Vol 342, October 30,
1993, p. 1067.
•Fourteen years are not enough that
responsible persons accepted this
proofs, but…
•At this moment, I believe that time for
vaccine production on BHK-21 cells for
human use, not only for rabies, is very
close.
Thank you for attention!