: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa.
View Article and Find Full Text PDFAntimicrob Agents Chemother
July 2014
Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease.
View Article and Find Full Text PDFDevelopment of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits.
View Article and Find Full Text PDFAntimicrob Agents Chemother
November 2013
Bacillus anthracis toxins can be neutralized by antibodies against protective antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax immunoglobulin), also known as AIGIV, derived from plasma of humans immunized with BioThrax (anthrax vaccine adsorbed), is under development for the treatment of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of AIGIV was assessed in naive animals and healthy human volunteers, and the efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolized B.
View Article and Find Full Text PDFAviat Space Environ Med
January 2010
Introduction: The use of hyperbaric oxygen (HBO) to expedite decompression from saturation has not been proven and may increase risk of toxicity to the pulmonary system. To evaluate any benefit of HBO during decompression, we used a 70-kg swine model of saturation and examined lung tissue by microarray analysis for evidence of RNA regulation.
Methods: Unrestrained, non-sedated swine were compressed to 132 fsw (5 ATA) for 22 h to achieve saturation.
Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components.
View Article and Find Full Text PDFBackground: Rapid resuscitation with oxygen-carrying fluids is critically important in hemorrhagic shock (HS) combat casualties in remote areas where blood is not available. Hemoglobin-based oxygen carrier-201 (HBOC-201) has been shown to increase survival and reduce immune activation following HS in animal models. Recombinant factor VIIa (rfVIIa), a systemic hemostatic agent, is Food and Drug Administration approved for use in acute hemorrhage in hemophilic patients.
View Article and Find Full Text PDFBackground: Some hemoglobin-based oxygen carriers (HBOCs) improve outcome in animal models of hemorrhagic shock (HS) in comparison with standard asanguinous resuscitation fluids. Nevertheless, concern about intrinsic vasoactivity, linked in part to low-molecular weight (MW) hemoglobin (Hb), has slowed HBOC development. We assessed the impact of decreasing the low-MW Hb component of bovine HBOC on vasoactivity in severe HS.
View Article and Find Full Text PDFPreviously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.
View Article and Find Full Text PDFOral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein.
View Article and Find Full Text PDFObjectives: To test our hypothesis that the hemoglobin based oxygen carrier HBOC-201 would have similar or superior efficacy to 6% hetastarch (HEX) as a pre-hospital 'bridging' fluid for hemorrhagic shock when delay to definitive medical care is prolonged to 24h.
Methods: Twenty-four pigs were anesthetized, instrumented, given a soft tissue injury, and bled 55% estimated blood volume. Pigs were randomized to receive HBOC-201, HEX, or no resuscitation fluids (NON).