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Tat-neutralizing antibodies in vaccinated macaques
Ilia Tikhonov1, Tracy J Ruckwardt, Glen S Hatfield
1Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
Journal of Virology
|February 14, 2003
Summary
Macaques immunized with HIV Tat protein or toxoid developed antibody responses. Sera recognized diverse Tat sequences, with Tat toxoid eliciting a more specific response, aiding in HIV vaccine development.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- The human immunodeficiency virus (HIV) Tat protein is crucial for viral replication and a potential vaccine target.
- Previous studies showed that immunizing macaques with Tat or modified Tat toxoid induced antibody responses.
Purpose of the Study:
- To compare the cross-reactivity of antisera from macaques immunized with Tat or Tat toxoid against diverse HIV Tat sequences.
- To identify linear epitopes recognized by these antisera.
Main Methods:
- Overlapping peptide arrays of clade B and C Tat sequences were used to map epitopes.
- Sera from immunized macaques were tested for reactivity against these peptide arrays.
- Monoclonal antibodies were used to assess the functional impact of epitope recognition.
Main Results:
- Sera from Tat-immunized macaques showed broad cross-reactivity with clade B and C Tat sequences, identifying a clade B-specific epitope.
- Sera from Tat toxoid-immunized macaques exhibited a more restricted recognition pattern, primarily reacting with clade B sequences, including a specific RPPQ motif.
- Antibodies targeting the N-terminus or RPPQ sequence inhibited Tat uptake and neutralized Tat activity.
Conclusions:
- Immunization with HIV Tat or Tat toxoid elicits distinct antibody profiles.
- The N-terminus and a specific RPPQ epitope are key targets for neutralizing antibodies against HIV Tat.
- These findings contribute to the development of effective HIV vaccines targeting the Tat protein.