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Most studies involving VRP vaccination have examined the ability of lovirus GP and/or NP to elicit protective immune responses. For example, a study by Hevey and colleagues demonstrated that a VRP expressing Marburg virus GP conveyed complete protection to cynomolgus monkeys infected with Marburg virus. Furthermore, enhanced levels of protection were observed when NP was also expressed.128 When a similar VRP-vaccination strategy was employed for Ebola virus, although VRPs expressing Ebola GP and/or NP were protective in rodents lethally challenged with Ebola virus,129 the vaccine was not protective in cynomolgus monkeys.18 This nding suggests that pathogenesis of Marburg and Ebola virus infection differs, perhaps with regard to infection course, tropism, and/or host responses. In a separate study, a bivalent VRP vaccine composed of the viral glycoproteins of both Lassa virus and Ebola virus proved to be protective in guinea pigs lethally challenged with Ebola virus. It should be noted that the vaccinated animals that did succumb to disease had no virus in their tissues upon post mortem analysis.130 Additional viral proteins, such as VP24, VP40, VP30, and VP35, have been explored as possible vaccine candidates. For example, VRPs expressing VP24 proved to be the best candidate to induce protection in BALB/c mice, with VP40 and VP30 yielding protection levels between 55% and 85% depending on dose numbers. In contrast, VP35 was the only protein offering protection in C57BL/6 mice.131 Recombinant vaccinia viruses expressing NP, VP35, VP40, or VP24 did not elicit protection in guinea pigs lethally challenged with Ebola virus.132,133 As the development of these types of vaccination strategies proceeds, it will be important to keep in mind that primate models remain essential for evaluation of these therapies for humans.

Echo [33]

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Li et al. [30]

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DNA vaccines represent another approach to elicit protection against Ebola virus. Plasmids encoding either Ebola virus GP, or NP, were shown to be protective in lethally challenged mice and guinea pigs.134,135 Working to improve the ef cacy of current replicon-based vaccination strategies, two groups have combined DNA vaccination with replicon administration in a prime boost manner. Sullivan and colleagues were successful in protecting macaques from challenge by administering a GP-expressing plasmid rst, followed by a boost with a GP-expressing adenoviral vector. Indeed, high antibody titers and increased cytotoxic T-lymphocyte (CTL) responses were observed in fully protected animals.136 A safety study involving 27 volunteers is underway for an initial evaluation of DNA primer vaccines in human subjects.137 Most recently, it was determined that immunization of nonhuman primates with only the adenoviral component (ADV-GP or ADV-NP) of this prime boost strategy induced a more rapid antibody response in animals, albeit less immunologically potent. Nonetheless, animals were protected against lethal challenge with virus.138 The rapidity of this vaccination strategy makes it an attractive candidate for the containment of sudden outbreaks of Ebola virus.

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Liu et al. [28]

Researchers have also examined the potential of heterologous live viral vectors in effectively preventing Ebola virus infection. Vesicular stomatitis virus (VSV)-based vectors are ne contenders, as VSV is known to elicit strong antibody and cellular immune responses.139 Rose and colleagues previously demonstrated that vaccination of mice with a recombinant VSV containing the glycoprotein of HIV-1 elicited high antibody titers as well as robust long-term memory and cellular immune responses.140,141 Based on this strategy, Feldmann and colleagues have generated a recombinant VSV vector expressing the Ebola virus GP. Protection against lethal challenge was conferred within a month and animals required only a single administration.30 7.7.4 Ebola Virus VLPs

signaled to the local media sub-system and lead to the relevant media drivers being closed, as do card removal events see Section 13.3.3.5.

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Liu et al. [31]

MultiMediaCards are miniature solid-state removable media cards about the size of a postage stamp. There are two main types: 1. 2. Read-only memory (ROM) cards Read/write cards which generally use Flash memory.

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