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Risk Assessment
Record information and status
Record ID
Date of creation
2014-01-22 20:13 UTC (gutemberg.sousa@mctic.gov.br)
Date of publication
2014-01-29 19:55 UTC (davi.bonavides@itamaraty.gov.br)

General Information
  • Brazil
Title of risk assessment
Risk Assessmejnt of of biological product for veterinary use, namely VECTORMUNE® FP-LT Fowl Pox and Laryngotracheitis vaccine
Date of the risk assessment
Competent National Authority(ies) responsible for the risk assessment
National Technical Biosafety Commission
Setor Policial Sul -SPO Área 5 Quadra 3 Bloco B - Térreo Salas 10 à 14
Brasília, DF
Brazil, CEP - 70610-200
Phone:(5561) 3411-5516
Fax:(5561) 3317-7475
Url:National Technical Biosafety Comission
Contact details of the main responsible risk assessor
Dra Maria Sueli Felipe Soares
National Technical Biosafety Comission (CTNBio)
Setor Policial Sul -SPO Área 5 Quadra 3 Bloco B - Térreo Salas 08 à 10
Brasília, DF
Brazil, CEP - 70610-200
Phone:(5561) 3411-5151
Fax:(5561) 3317-7475
Url:National Technical Biosafety Comission
Risk assessment details
Living modified organism
Dr Alexis Henry Gaetan Goux Production of medical or pharmaceutical compounds (human or animal) - Vaccines
Scope of the risk assessment
  • LMOs for Introduction into the environment
Risk assessment report / Summary
Methodology and points to consider
Potential adverse effects identified in the risk assessment
Fowl pox, also avian variola, is a disease caused by a virus and affects species of both domestic
and sylvan birds. It is a slow spreading disease, and may appear in either cutaneous,
diphtherial or systemic form. Fowl pox is caused by an enveloped DNA virus of the Avipoxvirus
genus belonging to the Poxviridae family, the Fowlpox virus (FPV). Avian poxvirus may infect
birds of all ages and races, both males and females, and has been described in over 200 bird
species. Clinical signs may vary according to the two forms, cutaneous or diphtheric, of the
disease. The cutaneous form displays lesions found in the featherless parts of the infected
birds. This form develops nodules, especially in the comb, eyelids, dewlaps and other
unfeathered bird parts. In company birds the disease may occur in the tarsus-metatarsus and
finger regions. The diphtheric form displays yellowish lesions in the mouth, esophagus and
tracheal mucosa and sometimes is followed by rheum.
Infectious laryngotracheitis (ILT) is an acute highly contagious chicken disease caused by
Infectious laryngotracheitis virus, namely ILT virus or ILTV, also classified as a member of the
Herpesviridae family, Alphaherpesvirinae subfamily. Genes were identified of this virus (gB and
UL32) that code for protective antigens and therefore are candidates for ideal vaccines, since
they induce a strong immune response to ILTV.
Likelihood that the potential adverse effects will be realized
GMO analysis according to Ruling Resolution nº 5, of March 12, 2008, Annex III
Studies on the effect of the viral sample in non-target species, on the viral distribution in target
species and on virus dissemination and multiplication showed that the sample FPV/ILT fails to
behave in any way different from the sample FPV, Cutter sample. To assess genetic stability,
five retro-passages in chicken were conducted and the recombinant remained stable.
Administration of the vaccine is indicated for 4 to 8 week chicken. Several studies were carried
out to assess whether the behavior of the recombinant virus varies from that of the parental
vaccine. All parameters assessed showed that the biological features are not different from
that of the parental virus, regarding both in vivo replication and tissue tropism.
As far as animal health is concerned, the following tests were conducted:
1. Safety test in commercial poultry (normal dose);
2. Safety test in commercial egg-layer poultry and slaughter matrices (normal dose);
3. Safety test (10 x normal dose) in 6 week susceptible poultry;
4. Safety test associated to viral lateral transmission of immunized to non-immunized
5. Safety test in different fowl species (quails, doves and turkeys);
6. Safety test in other non-avian species;
7. Assessment of tissue tropism in susceptible host; and
8. Master Seed Virus (MSV) retro-passage study of the recombinant vaccine.
No adverse reaction was found in the use of this vaccine.
The vaccine may be held as safe for human health, since there are no reports of productive
infection caused by FPV in any non-avian species. The FPV vaccine strain (receptor) has been
used around the world as a commercial vaccine for birds with no record of adverse effect
and/or risks to public health.
Estimation of the overall risk
Fowl pox virus (FPV), Cutter sample, is the origin of most live vaccines against avian variola.
Two ILT genes, UL-32 and Gb, were introduced in this virus, in addition to a marker gene Lac Z,
from E. coli, using two synthetic promoters and a region where an homologous recombination
may occur with FPV. The Gb gene of ILT mediates the viral penetration through fusion and
gene UL-32 carries the pre-assembled capsides to the DNA packing sites.
To achieve this result, a 3 kb fragment of FPV genomic DNA was cloned on the pUC18 vector.
An internal fragment of 175 pb was removed and replaced by a construct containing gene
UL-32 with the synthetic PS promoter, followed by gene lacZ directed by the synthetic
promoter P17 and followed by gene gB also directed by the synthetic promoter PS. Synthetic
promoters PS and P17 emulate the consensus early/late promoter and the early poxvirus
promoter, respectively. Several cloning phases were conducted before the final construct was
completed. Genes gG and UL32 code for the LTV protective antigens, while gene lacZ operates
as a reporter gene to make the recombinant viruses selection. This construct, carried out in
pUC18, was used in the homologous recombination with the parental FPV strain, during the
process of chicken embryo fibroblasts cells replication. Plates expressing gene lacZ were
isolated and selected until a pure recombinant gene was obtained. Homologous recombination
was confirmed by Southern blot using probes that hybridized in both sides of the insertion site.
DNA sequencing was also conducted. Expression of genes UL32 and gB was confirmed by
Western blot.
Receiving environment(s) considered
- Environmental Safety

The analysis of data related to vaccine stability, non-reversion to virulence on passages in the
target organism, inability to keep in the environment and host limitation leads to a conclusion
that the vaccine is environmentally safe.
- Post Commercial Release Safety Monitoring Plan
The company informs that post-commercial release monitoring, following the vaccine
registration, shall be conducted under a drug-vigilance system and reported to CTNBio should
any adverse effects appear.
4. Final Opinion
The analysis of data related to vaccine stability, non-reversion to virulence on passages in the
target organism, inability to keep in the environment and host limitation leads to a conclusion
that the vaccine is environmentally safe. Considering the effective and safe use of FPV in
vaccines all over the world for over four decades and lack of evidence suggesting a different
behavior of the recombinant form as against the parental form, we are favorable to approval
of the within application for the purposes as requested. Therefore, we conclude that the
activity is not a potential cause of significant degradation of the environment, nor harmful to
human and animal health
LMO detection and identification methods proposed
Molecular Traditional Methods

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