Proposed Animal Study to Evaluate Simian Foamy Virus SFV Transmission by Blood

1
Proposed Animal Study to Evaluate Simian Foamy
Virus (SFV) Transmission by Blood

• Arifa S. Khan, Ph.D.
• DVP, OVRR, CBER, FDA
• BPAC, December 13, 2001

2
Overall Summary of Planned Study

• Whole blood from an SFV-infected rhesus macaque
  will be injected into SFV-negative monkeys.
• Blood recipients will be monitored for SFV
  infection by virological, serological, molecular
  and clinical analysis.
• The inoculated animals will be followed for 1
  year to evaluate SFV infection by blood.

3
Donor Criteria

• Adult, rhesus macaque from which SFV has been
  well-characterized (biologically and
  molecularly).
• - Exist in-house from previous studies
• High viral load in plasma and/or PBMCs.
• - TaqMan PCR for SFV
• Good replication efficiency.
• - in vitro analysis in different human cell
  lines

4
Selection of SFV Negative Animals as Blood
Recipients

• Juvenile, rhesus macaques will be obtained from a
  known retrovirus-free colony and the absence of
  SRV, STLV and SIV confirmed by independent
  analysis.
• SFV negative animals will be identified by
  serology and confirmed by PCR and culture.
• Animals will be individually-housed at the time
  of initial serology and maintained as such
  throughout study.

5
Experimental Details of Monkey Study to Evaluate
SFV Transmission by Blood

• Animals SFV -ve Rhesus macaques
• 6 transfused with SFV blood
• 2 transfused with SFV- blood
  (controls)
• Inoculum blood volume for intravenous
  transfusion will be determined according to body
  weight
• Blood Preservative CPD-adenine (currently used
  in human blood transfusions)
• Plasma and PBMCs will be prepared and stored from
  every blood collection
• Experimentally negative animals will be
  challenged with a laboratory stock of SFV

6
Monitoring of SFV Infection in Blood Recipients

• Serology
• - neutralizing antibody titer
• - Western blot
• Virology
• - SFV detection in monkey PBMCs by PCR
  and
• virus identification by sequencing
• - virus isolation by co-culture of
  monkey PBMCs
• with Mus dunni cells

7
Additional Evaluation of Monkeys Transfused with
SFV Blood

• Clinical monitoring
• - Hematology
• - Serum chemistry
• - physical exam
• Toxicology
• Histology
• Immunophenotyping

8
STUDY OUTCOME

• The results of the proposed study will provide a
  scientific basis for evaluating potential risk of
  SFV transmission by blood transfusion and help
  formulate criteria for acceptance or exclusion of
  potential blood donors who are at risk for SFV
  infection.