Showing papers by "Michael J. Caulfield published in 2003"
TL;DR: Results are suggestive of an immunization strategy for humans that is centered on use of the adenovirus vector and in which existing adenavirus immunity may be overcome by combined immunization with adjuvanted DNA and adenvirus vector boosting.
Abstract: Cellular immune responses, particularly those associated with CD3 CD8 cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defective adenovirus serotype 5 (Ad5) vector, each expressing the same codon-optimized HIV-1 gag gene for immunogenicity in rhesus monkeys. The DNA vaccines were formulated with and without one of two chemical adjuvants (aluminum phosphate and CRL1005). The Ad5-gag vector was the most effective in eliciting anti-Gag CTL. The vaccine produced both CD4 and CD8 T-cell responses, with the latter consistently being the dominant component. To determine the effect of existing antiadenovirus immunity on Ad5-gag-induced immune responses, monkeys were exposed to adenovirus subtype 5 that did not encode antigen prior to immunization with Ad5-gag. The resulting anti-Gag T-cell responses were attenuated but not abolished. Regimens that involved priming with different DNA vaccine formulations followed by boosting with the adenovirus vector were also compared. Of the formulations tested, the DNA-CRL1005 vaccine primed T-cell responses most effectively and provided the best overall immune responses after boosting with Ad5-gag. These results are suggestive of an immunization strategy for humans that are centered on use of the adenovirus vector and in which existing adenovirus immunity may be overcome by combined immunization with adjuvanted DNA and adenovirus vector boosting.
425 citations
TL;DR: A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay, which had greater sensitivity and a wider dynamic range.
Abstract: The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.
277 citations
TL;DR: It is shown that the ELISPOT assay performed best when testing peripheral blood mononuclear cells that had been isolated and then frozen on the same day as blood was drawn, and that freezing PBMCs from blood that was stored overnight before processing resulted in dramatically reduced responses.
Abstract: An interferon-gamma ELISPOT assay has been developed for assessment of cellular immune responses to Varicella-Zoster Virus (VZV) in large, multi-center clinical vaccine trials. We show that the assay performed best when testing peripheral blood mononuclear cells (PBMCs) that had been isolated and then frozen on the same day as blood was drawn, and that freezing PBMCs from blood that was stored overnight before processing resulted in dramatically reduced responses. This assay was used to monitor cell-mediated immunity (CMI) in response to a booster immunization with an investigational live, attenuated VZV vaccine in an elderly population that had been vaccinated 8–10 years previously. The booster vaccine elicited a 1.6- to 1.7-fold rise in the VZV-specific cellular immune response as measured by the ELISPOT assay. The increase from pre to post booster vaccination response was more pronounced (∼ 2.2-fold rise) in a subset of subjects who had received two prior immunizations with a live, attenuated vaccine. J. Med. Virol. 70:S38–S41, 2003. © 2003 Wiley-Liss, Inc.
52 citations
TL;DR: It is indicated that aluminum phosphate is highly effective at delivering an antigen (HBsAg) together with TH1 adjuvants such as IL-12 and GACGTT resulting in a shift from a TH2 to a TH1 response.
22 citations
Patent•
30 Jul 2003TL;DR: In this paper, a novel method is provided, for use within serological or screening assays, wherein microbial colonies are grown on filter membranes in multi-well plates, enabling the colonies to be stained, imaged, and counted automatically using such automated systems as, e.g., computer and video-based imaging systems.
Abstract: A novel method is provided, for use within serological or screening assays, wherein microbial colonies are grown on filter membranes in multi-well plates. This process enables the colonies to be stained, imaged, and counted automatically using such automated systems as, e.g., computer and video-based imaging systems.
7 citations