BHK21 RABIES VACCINE A CANDIDATE VACCINE FOR HUMANS

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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

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Country Report In the North community Subotica, a
trial of oral vaccination started by delta-planes
sponsored by VIRBAC
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BHK-21 C 13 cell culture is well known substrate
for animal rabies vaccine production
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BHK-21 C 13 cells are much better producers of
rabies virus than HDC or VERO cells
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Baer G.M. Improvements in Rabies Post-Exposure
Treatment, Dubrovnik, Yugoslavia, 1984, pp.
15-24 Only BHK-21 rabies vaccine induced
interferon (in mice and monkeys), HDC did not!
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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 in-house 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...
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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? Its a question of the WHO and we
have the first answer from late professor Sureau
Nero
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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
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Yes, we regularly induced tumor on the
inoculation site of suspension of BHK 21 cell
culture, but
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tumor is solitary, enormous, and never produced
metastases.
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Tumor cells are very similar as BHK 21 C 13 in
vitro,
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• Summary of tumorigenicity of BHK-21 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 Its 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.

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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.

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We accepted their opinions and started with
en-house rabies vaccine production in Pasteur
Institute in Novi Sad, Serbia, for human use,
named YU BHK Rabivak.
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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
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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
2.6 IU/ml
5 th July 2006
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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.

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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.

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• 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!