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186a Prime-Boost Immunisation Leads to the Development of a Persistent, High Avidity CD8 T-Cell Population
M. J. Estcourt1, A. Brookes2, A. J. Ramsay3, S. A. Thomson1, C. J. Medveckzy1, and I. A. Ramshaw*1
1John Curtin Sch. of Med. Res., Australian Natl. Univ., Canberra; 2Univ. of Melbourne, Australia; and 3Ctr. for Biomolecular Vaccine Technology, Univ. of Newcastle, Australia
The vaccination strategy known as “prime-boost” immunisation, which involves priming the immune system with DNA and then “boosting” the response with a recombinant poxvirus encoding the same antigens, leads to the induction of high levels of cell-mediated immunity, which is thought to play an essential role in the control of many intracellular agents, including HIV. We have established that the efficacy of this vaccination strategy lies in its unique ability to induce T-cell populations of high avidity for the immunising antigen. Prime-boost immunisation generated CTL populations of high avidity that upon challenge represented over 30% of the total CD8+ T-cell population, unlike those in animals given either DNA or poxvirus vaccines. CTL avidity was also directly and strikingly demonstrated in vivo using a novel assay that monitors the depletion of target cells labelled with immunogenic peptide and vital dye. This generation of antigen-specific T cells of high avidity may result in the early detection of infected cells, offering hope for the development of effective prophylaxis against pathogens such as HIV, which have presented major problems for vaccine development.
