Vical Incorporated has announced that antigen-specific memory T-cell responses to cytomegalovirus (CMV), which may be important in protecting against CMV disease, were detected six months after DNA vaccination in a majority of CMV-seronegative subjects in a previously completed phase 1 study. Memory T-cells are known to respond quickly upon subsequent infection with virus, transforming into active, effector T-cells that can control disease.
The company previously detected transient vaccine-induced effector T-cells in a minority of subjects in the same phase I study using an ex vivo Elispot assay. The recent results were obtained with a highly sensitive alternative assay, a cultured Elispot assay, which detects memory T-cells. "We are seeing a growing body of evidence that assays measuring only effector immune responses may underestimate the extent of T-cell priming by DNA vaccination," said Larry Smith, Ph.D., Vical's vice president of vaccine research. "An assay that measures pathogen-specific immune memory may provide a more meaningful metric for DNA vaccines. We view the cultured Elispot assay results as an important step toward understanding responses to DNA vaccination in humans and in advancing DNA vaccines toward approval."
The highly sensitive cultured interferon-gamma Elispot assay detected memory T-cell immune responses in 15 of 22 CMV-seronegative subjects (68%) using archived samples from the company's completed Phase 1 trial of its bivalent DNA vaccine encoding CMV phosphoprotein 65 (pp65) and glycoprotein B (gB). Memory T-cell responses against these antigens were detected 10 to 12 weeks after the first vaccine dose and persisted for at least 24 weeks after the last vaccine dose (the last point in time for which specimens were available). Antigen-specific memory responses were detected by the cultured Elispot assay in some subjects who failed to show effector T-cell responses at any point in time by an ex vivo Elispot assay.