Recombinant modified vaccinia virus Ankara–simian immunodeficiency virusgag polelicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

Abstract

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)͞rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIV SM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8؉ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I͞peptide tetramer. These Gag epitopespecific CD8؉ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.

A Nonhuman Primate Model for the Selective Elimination of CD8+ Lymphocytes Using a Mouse-Human Chimeric Monoclonal Antibody

“…The p11C-specific CTL were evaluated using the flow cytometry-based tetramer technology as described previously. 13,14 Whereas the addition of a control monoclonal antibody had no effect on the expansion of virus-specific CTL, addition of cM-T807 caused nearly complete inhibition of SIV Gag peptide p11C-specific CTL expansion ( Figure 1B).…”

“…To quantitate expansion of SIVmac peptide-specific CD8ϩ T cells, the cells were washed and stained with anti-rhesus monkey CD3 (FN-18; gift of David M. Neville, Jr., National Institutes of Health, Bethesda, MD) directly coupled to APC and PE-coupled tetrameric complexes of Mamu-A*01/p11C, C-M as described previously. 13,14 The percentage of T cells binding tetramer was then evaluated by flow cytometry.…”

Immunodomination in the Evolution of Dominant Epitope-Specific CD8+ T Lymphocyte Responses in Simian Immunodeficiency Virus-Infected Rhesus Monkeys

“…Although HIV vaccine strategies designed to elicit a high frequency of CD8 ϩ T lymphocytes are being pursued, little attention has been paid to the breadth of these immune responses. Because vaccine-induced CD8 ϩ T lymphocytes mediate control of viremia and therefore slow clinical progression in SIV-or simian human immunodeficiency virus (SHIV)-infected rhesus monkeys (13)(14)(15)(16), investigators are developing vaccine modalities that increase the magnitude of virus-specific CD8 ϩ T lymphocyte responses (17). However, an effective vaccine-elicited CD8 ϩ T lymphocyte response must recognize a diversity of epitopes so as to minimize the impact of individual viral epitope escape mutations.…”

Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses

“…A variety of attenuated pox viruses are being examined as vectors for use as either single modality vaccines or as boosting immunogens in association with heterologous priming immunizations (6)(7)(8)(9)(10)(11)(12)(13)(14). These pox vectors include a number of avian pox viruses as well as various attenuated vaccinia viruses (10)(11)(12)(13)(14). It is, however, unclear whether one of these pox vectors is superior to another for use in this context.…”