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High Species Density Patterns In Macrofaunal Invertebrate Communities In The Marine Benthos, John Oliver, Kamille Hammerstrom, Erika Mcphee-Shaw, Peter Slattery, James Oakden, Stacy Kim, S. Ian Hartwell

United States Department of Commerce: Staff Publications

Species density of macrofaunal invertebrates living in marine soft sediments was highest at the shelf-slope break (100–150 m) in Monterey Bay (449 m^-2). There were 337 species m^-2 in the mid-shelf mud zone (80 m). There were fewer species along the slope: 205 m^-2 from the lower slope (950-2000 m) and 335 m^-2 on the upper slope (250-750 m). Species density was highest inside the bay (328-446 m^-2) compared to outside (336-339 m^-2), when examining samples at selected water depths (60-1000 m). There was little difference in local species density from …

Ontogenetic Dietary Information Of The California Sea Lion (Zalophus Californianus) Assessed Using Stable Isotope Analysis, Anthony J. Orr, Seth D. Newsome, Jeffrey L. Laake, Glenn R. Vanblaricom, Robert L. Delong

United States Department of Commerce: Staff Publications

We used stable carbon (δ¹³C) and nitrogen (δ¹⁵N) isotopes to examine ontogenetic dietary changes in 289 California sea lions (Zalophus californianus) at San Miguel Island, California during 2004–2007. Tissues analyzed included fur, red blood cells, plasma, and serum. For all tissues, pups had higher δ¹⁵N values and lower δ¹³C values compared to adults, which indicated that pups were feeding higher trophically than older conspecifics and on a lipid-rich milk diet prior to weaning. Yearling δ¹⁵N values were slightly lower than pup or nearly indistinguishable from adult values depending …

The Effect Of Stimulation Frequency On The Transmural Ventricular Monophasic Action Potential In Yellowfin Tuna Thunnus Albacares, S. M. Patrick, E. White, R. W. Brill, H. A. Shiels

United States Department of Commerce: Staff Publications

Monophasic action potentials (MAPs) were recorded from the spongy and compact layers of the yellowfin tuna Thunnus albacares ventricle as stimulation frequency was increased. MAP duration decreased with increase in stimulation frequency in both the spongy and compact myocardial layers, but no significant difference in MAP duration was observed between the layers.

A Simple Photograph-Based Approach For Discriminating Between Free-Ranging Long-Finned (Globicephala Melas) And Short-Finned (G. Macrorhynchus) Pilot Whales Off The East Coast Of The United States, Brenda K. Rone, Richard M. Pace Iii

United States Department of Commerce: Staff Publications

Line transect based abundance estimation is complicated for long-finned (LFPW, Globicephala melas) and short-finned (SFPW, G. macrorhynchus) pilot whales because of their similarity in appearance and their overlapping summertime range in some areas.We developed a photograph-based approach to distinguish between species of free-ranging pilot whales in the northwest Atlantic.We collected skin samples and photographs during the summers of 2004–2007 and used skin samples to distinguish species based on mitochondrial DNA. Relative morphometric measurements from photographs were examined using mixed-effect models and logistic regression. The best model among 94 candidate models had an overall classification error rate of 2.5%. …

Evidence Of Susceptibility To Morbillivirus Infection In Cetaceans From The United States, T. K. Rowles, L. S. Schwacke, R. S. Wells, J. T. Saliki, L. Hansen, A. Hohn, F. Townsend, R. A. Sayre, A. J. Hall

United States Department of Commerce: Staff Publications

Cetacean morbilliviruses (CeMV) are viruses that can cause mass mortalities among various odontocete species. In this study levels of “herd” immunity in cetaceans from the U.S. coast are described from the distribution and prevalence of antibodies against morbilliviruses. Neutralizing antibody titers against dolphin morbillivirus (DMV), porpoise morbillivirus (PMV), phocine distemper (PDV), and canine distemper viruses (CDV) were measured. Positive samples had higher titers against the CeMV than against the other morbilliviruses tested, indicating that although PDV or CDV can be used to investigate exposure their use may result in a higher false negative rate. The results suggest that morbillivirus did …

Defining Bottlenose Dolphin (Tursiops Truncatus) Stocks Based On Environmental, Physical, And Behavioral Characteristics, Jacalyn L. Toth, Aleta A. Hohn, Kenneth W. Able, Antoinette M. Gorgone

United States Department of Commerce: Staff Publications

The population structure of bottlenose dolphins, Tursiops truncatus, along the U.S. Atlantic coast has recently been redefined from one homogenous population into five coastal stocks. Local studies indicate even finer structure, primarily based on isolation of dolphins inhabiting estuaries.We identified population structuring of non-estuarine coastal bottlenose dolphins during a study in New Jersey, the northern range along the Atlantic Coast. Using photo-identification and distribution survey results, an analysis identified two major clusters of individuals significantly separated by five variables (distance from shoreline, group size, occurrence of the barnacle Xenobalanus globicipitis, avoidance behavior, and individual coloration). Sightings assigned to …

Individual Variation In Pup Vocalizations And Absence Of Behavioral Signs Of Maternal Vocal Recognition In Weddell Seals (Leptonychotes Weddellii), Ilse C. Van Opzeeland, Sofie M. Van Parijs, Stephan Frickenhaus, Cornelia M. Kreiss, Olaf Boebel

United States Department of Commerce: Staff Publications

Individually stereotyped vocalizations often play an important role in relocation of offspring in gregarious breeders. In phocids, mothers often alternate between foraging at sea and attending their pup. Pup calls are individually distinctive in various phocid species. However, experimental evidence for maternal recognition is rare. In this study, we recorded Weddell seal (Leptonychotes weddellii) pup vocalizations at two whelping patches in Atka Bay, Antarctica, and explored individual vocal variation based on eight vocal parameters. Overall, 58% of calls were correctly classified according to individual. For males (n = 12) and females (n = 9), respectively, nine …

Calculating Ne And Ne/N In Age-Structured Populations: A Hybrid Felsenstein-Hill Approach, Robin Waples, Chi Do, Julien Chopelet

United States Department of Commerce: Staff Publications

The concept of effective population size (N_e) was developed under a discrete generation model, but most species have overlapping generations. In the early 1970s, J. Felsenstein and W. G. Hill independently developed methods for calculating N_e in age structured populations; the two approaches produce the same answer under certain conditions and have contrasting advantages and disadvantages. Here, we describe a hybrid approach that combines useful features of both. Like Felsenstein’s model, the new method is based on age specific survival and fertility rates and therefore can be directly applied to any species for which life table …

Incidence Of Tricyclic Antidepressant-Like Complications After Cyclobenzaprine Overdose, Vikhyat S. Bebarta, Joseph Maddry, Douglas J. Borys, David L. Morgan

Uniformed Services University of the Health Sciences

Background: The cyclobenzaprine structure is similar to amitriptyline; however, tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been reported. Our objective was to determine the incidence of TCA-like effects in cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We compared the incidence of these effects to amitriptyline overdoses collected during the same period.

Methods: We performed a retrospective review of 2 years of cases as reported to the Texas Poison Center Network. We identified sole ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical outcome and clinical effect. A trained reviewer used a standard data …

Pre-Clinical Screening Of Immunomodulatory Compounds Using The Parent-Into-F1 Model, Charles S. Via

Uniformed Services University of the Health Sciences

Activation of the innate immune system by toll-like receptors (TLR) provides an early response to pathogens and shapes the subsequent antigen-specific adaptive immune response. Unmethylated cytosine-guanine dinucleotide (CpG)motifs present in bacterial DNA, but not vertebrate DNA, can be detected by Toll like receptor 9 (TLR9)—bearing DC and B cells resulting in a pro-inflammatory Th1 response. Synthetic oligodeoxynucleotides (ODN) expressing these CpG motifs exhibit similar in vivo biologic activity and have been shown to reduce disease severity for selected pathogens, to promote vaccine responses and to enhance anti-tumor responses (reviewed in Ref.). Conversely, suppressive DNA sequences have also been identified. TTAGGG …

Morphine-Induced Modulation Of Ltd At Gabaergic Synapses In The Ventral Tegmental Area, Matthieu Dacher, Fereshteh S. Nugent

Uniformed Services University of the Health Sciences

Adaptive behaviors often require the learning of appropriate responses to rewarding stimuli, yet aberrant learning processes can lead to serious diseases such as addiction. Dopamine (DA) neurons of the ventral tegmental area (VTA) play an essential role in the treatment of rewarding stimuli, and they exhibit plasticity in response to such stimuli, but also to drugs of abuse. Previously we discovered a form of presynaptic nitric oxide (NO)-mediated long-term potentiation (LTP_GABA) at GABAergic synapses onto VTA DA neurons that is prevented with morphine in vivo 24 h after exposure. Here we investigated whether the same GABAergic synapses are …

Anti-Fcεr1 Antibody Injections Activate Basophils And Mast Cells And Delay Type 1 Diabetes Onset In Nod Mice, Marc P. Hübner, David Larson, Marina N. Torrero, Ellen Mueller, Yinghui Shi, Kristin E. Killoran, Edward Mitre

Uniformed Services University of the Health Sciences

Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevent diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In …

Opiates And Plasticity, Matthieu Dacher, Fereshteh S. Nugent

Uniformed Services University of the Health Sciences

Opiates are among the most powerful analgesics and pain-relieving agents. However, they are potentially extremely addictive thereby limiting their medical use, making them exceedingly susceptible to abuse and adding to the global drug problem. It is believed that positive memories associated with the pleasurable effects of opiates and negative memories associated with dysphoria during opiate withdrawal contribute to compulsive opiate-seeking behavior characterizing addiction. There is a vast amount of available data regarding the neuroadaptations in response to opiates during opiate tolerance, dependence and withdrawal that contribute to opiate addiction, yet it is still a major challenge to identify the neurobiological …

Accelerated Lymphocyte Reconstitution And Long-Term Recovery After Transplantation Of Lentiviral-Transduced Rhesus Cd34+ Cells Mobilized By G-Csf And Plerixafor, Naoya Uchida, Aylin Bonifacino, Allen E. Krouse, Mark E. Metzger, Gyorgy Csako, Agnes Lee-Stroka, Ross M. Fasano, Susan F. Leitman, Joseph J. Mattapallil, Matthew M. Hsieh, John F. Tisdale, Robert E. Donahue

Uniformed Services University of the Health Sciences

Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34⁺ cells in rhesus macaques. We sought to evaluate whether these CD34⁺ cells can stably reconstitute blood cells with lentiviral gene marking.

Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34⁺ cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.

Results. G-CSF and plerixafor mobilization resulted in CD34⁺ cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) …

Arachidonyl Trifluoromethyl Ketone Ameliorates Experimental Autoimmune Encephalomyelitis Via Blocking Peroxynitrite Formation In Mouse Spinal Cord White Matter, Adam C. Vana, Shihe Li, Rachel Ribeiro, Flaubert Tchantchou, Yumin Zhang

Uniformed Services University of the Health Sciences

Inhibition of phospholipase A₂ (PLA₂) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA₂ inhibition are still not well understood. In this study, we found that cytosolic PLA₂ (cPLA₂) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. Although cPLA₂ is also expressed in spinal cord neurons and oligodendrocytes, there were no differences observed in these cell types between EAE and control animals. Arachidonyl trifluoromethyl ketone (AACOCF3), …

Book Review: Why People Get Lost: The Psychology And Neuroscience Of Spatial Cognition By Paul A. Dudchenko, Ilana R. Yurkiewicz, Jack W. Tsao

Uniformed Services University of the Health Sciences

Why People Get Lost demands no specialized knowledge of neuroscience, as its inside flap advertises. This is true to an extent; the book is an academic behemoth of research and data, but Dudchenko guides the reader through it with engaging anecdotes that inject a personal flair into the hard science. He writes with a refreshing directness, beginning each new subject with an introduction that tells the reader: this is what you are going to learn, this is how I am going to show you, and this is why you should care. If wayfinding intrigues you without preamble, it may not …

Comparison Of Combat Gauze And Traumastat In Two Severe Groin Injury Models, Françoise Arnaud, Kohsuke Teranishi, Tomoaki Okada, Dione Parreño-Sacdalan, Daniel Hupalo, George Mcnamee, Walter Carr, David Burris, Richard Mccarron

Uniformed Services University of the Health Sciences

Background. Fabric-like hemostatic dressings offer promise for hemorrhage control in noncompressible areas, especially given their similarity in form to standard gauze currently in use. Recently, two such products, Combat Gauze (CBG) and TraumaStat (TMS), were introduced. Their performance is evaluated in two vascular injury models.

Materials andMethods. The dressings were evaluated in anesthetized Yorkshire pigs, hemorrhaged by full transection of the femoral vasculature with 2 min free bleeding period (CBG = 6, TMS = 6) or by 4 mm femoral arterial puncture with 45 s free bleeding period (CBG = 8, TMS = 8). After injury, dressings were applied, followed …

Effectiveness Of Battlefield-Ethics Training During Combat Deployment: A Programme Assessment, Christopher H. Warner, George N. Appenzeller, Angela Mobbs, Jessica R. Parker, Carolynn M. Warner, Thomas Grieger, Charles W. Hoge

Uniformed Services University of the Health Sciences

Background Breakdowns in the ethical conduct of soldiers towards non-combatants on the battlefi eld are of grave concern in war. Evidence-based training approaches to prevent unethical conduct are scarce. We assessed the eff ectiveness of battlefi eld-ethics training and factors associated with unethical battlefi eld conduct.

Methods The training package, based on movie vignettes and leader-led discussions, was administered 7 to 8 months into a 15-month high-intensity combat deployment in Iraq, between Dec 11, 2007, and Jan 30, 2008. Soldiers from an infantry brigade combat team (total population about 3500) were randomly selected, on the basis of company and the …

Startle Response Related Genes, Lei Zhang, Xian-Zhang Hu, He Li, Xiaoxia Li, Stanley Smerin, David M. Benedek, Robert Ursano

Uniformed Services University of the Health Sciences

The startle reaction (also known as the startle response, the startle reflex, or the alarm reaction) is the psychological and physiological response to a sudden unexpected stimulus, such as a flash of light, a loud noise (acoustic startle reflex), or a quick movement near the face. Abnormalities of startle response have been observed in many stress-related mental disorders, such as schizophrenia and post-traumatic stress disorder (PTSD). However, the molecular mechanisms of startle in stress-associated conditions – for example, whether the startle reaction is associated with any gene variance – is still unknown. In this paper, we will carry out a …

Liposome-Induced Complement Activation And Related Cardiopulmonary Distress In Pigs: Factors Promoting Reactogenicity Of Doxil And Ambisome, János Szebeni, Péter Bedőcs, Zoltán Rozsnyay, Zsóka Weiszhár, Rudolf Urbanics, László Rosivall, Rivka Cohen, Olga Garbuzenko, György Báthori, Miklós Tóth, Rolf Bünger, Yechezkel Barenholz

Uniformed Services University of the Health Sciences

Hypersensitivity reactions to liposomal drugs, often observed with Doxil and AmBisome, can arise from activation of the complement (C) system by phospholipid bilayers. To understand the mechanism of this adverse immune reaction called C activation-related pseudoallergy (CARPA), we analyzed the relationship among liposome features, C activation in human serum in vitro, and liposome-induced cardiovascular distress in pigs, a model for human CARPA. Among the structural variables (surface charge, presence of saturated, unsaturated, and PEGylated phospholipids, and cisplatin vs. doxorubicin inside liposomes), high negative surface charge and the presence of doxorubicin were significant contributors to reactogenicity both in vitro and …

Fibroblast Growth Factor 1 (Fgfr1) Modulation Regulates Repair Capacity Of Oligodendrocyte Progenitor Cells Following Chronic Demyelination, Yong-Xing Zhou, Ravinder Pannu, Tuan Q. Le, Regina C. Armstrong

Uniformed Services University of the Health Sciences

The adult mammalian brain contains multiple populations of endogenous progenitor cell types. However, following CNS trauma or disease, the regenerative capacity of progenitor populations is typically insufficient and may actually be limited by non-permissive or inhibitory signals in the damaged parenchyma. Remyelination is the most effective and simplest regenerative process in the adult CNS yet is still insufficient following repeated or chronic demyelination. Our previous in vitro studies demonstrated that fibroblast growth factor receptor 1 (FGFR1) signaling inhibited oligodendrocyte progenitor (OP) differentiation into mature oligodendrocytes. Therefore, we questioned whether FGFR1 signaling may inhibit the capacity of OP cells to generate …

Cannabinoid Receptor Expression And Phosphorylation Are Differentially Regulated Between Male And Female Cerebellum And Brain Stem After Repeated Stress: Implication For Ptsd And Drug Abuse, Guoqiang Xing, Janis Carlton, Lei Zhang, Xiaolong Jiang, Carol Fullerton, He Li, Robert Ursano

Uniformed Services University of the Health Sciences

Recent study demonstrated a close relationship between cerebellum atrophy and symptom severity of pediatric maltreatment-related posttraumatic stress disorder (PTSD). It has also been known that females are more vulnerable than males in developing anxiety disorders after exposure to traumatic stress. The mechanisms are unknown. Because cannabinoid receptors (CB₁ and CB₂) are neuroprotective and highly expressed in the cerebellum, we investigated cerebellar CB expression in stressed rats. Young male and female Sprague-Dawley rats were given 40 unpredictable electric tail-shocks for 2 h daily on 3 consecutive days. CB₁ and CB₂ mRNA and protein levels in rat …

Valproic Acid Inhibits Neurosphere Formation By Adult Subventricular Cells By A Lithium-Sensitive Mechanism, Q. Zhou, C. L. Dalgard, C. Wynder, M. L. Doughty

Uniformed Services University of the Health Sciences

The mood stabilizer valproic acid (VPA) decreases neural progenitor proliferation and promotes neurogenesis in the adult hippocampus. However, the effects of VPA on progenitor cells in the adult subventricular zone (SVZ) are not as well characterized. Here we report VPA blocks neurosphere formation and inhibits DNA synthesis in cultured NSCs from the SVZ of adult mice. Inhibition of DNA synthesis is associated with the up-regulation of the differentiation transcription factors Egr1 and Neurod1 and down-regulation of transcription factors associated with “stemness”. Co-treatment of VPA with the mood stabilizer lithium antagonizes the anti-proliferative effects of VPA on adult NSCs and abolishes …

Distinct Role Of Nitric Oxide And Peroxynitrite In Mediating Oligodendrocyte Toxicity In Culture And In Experimental Autoimmune Encephalomyelitis, S. Li, A. C. Vana, R. Ribeiro, Y. Zhang

Uniformed Services University of the Health Sciences

Nitric oxide has been implicated in the pathogenesis of multiple sclerosis. However, it is still unclear whether nitric oxide plays a protective role or is deleterious. We have previously shown that peroxynitrite, a reaction product of nitric oxide and superoxide, is toxic to mature oligodendrocytes (OLs). The toxicity is mediated by intracellular zinc release, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), activation of 12-lipoxygenase (12-LOX) and the formation of reactive oxygen species (ROS). In this study, we found that the donors of nitric oxide, dipropylenetriamine NONOate (DPT NONOate) and diethylenetriamine NONOate (DETA NONOate), protected OLs from peroxynitrite or zinc-induced toxicity. …

Regulation Of C-Type Natriuretic Peptide Expression, Donald F. Sellitti, Nancy Koles, Maria C. Mendonça

Uniformed Services University of the Health Sciences

C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid …

In Vitro Profiling Of Epigenetic Modifications Underlying Heavy Metal Toxicity Of Tungsten-Alloy And Its Components, Ranjana Verma, Xiufen Xu, Manoj K. Jaiswal, Cara Olsen, David Mears, Giuseppina Caretti, Zygmunt Galdzicki

Uniformed Services University of the Health Sciences

Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma(SKNMC), and mousemyoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50–200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calciumchannel …

Development Of Dengue Dna Vaccines, Janine R. Danko, Charmagne G. Beckett, Kevin R. Porter

Uniformed Services University of the Health Sciences

Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical …

A Recombinant Hendra Virus G Glycoprotein-Based Subunit Vaccine Protects Ferrets From Lethal Hendra Virus Challenge, Jackie Pallister, Deborah Middleton, Lin-Fa Wang, Reuben Klein, Jessica Haining, Rachel Robinson, Manabu Yamada, John White, Jean Payne, Yan-Ru Feng, Yee-Peng Chan, Christopher C. Broder

Uniformed Services University of the Health Sciences

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in …

A Systematic Review Of Experimental Infections With Enterotoxigenic Escherichia Coli (Etec), Chad K. Porter, Mark S. Riddle, David R. Tribble, A. Louis Bougeois, Robin Mckenzie, Sandra D. Isidean, Peter Sebeny, Stephen J. Savarino

Uniformed Services University of the Health Sciences

Volunteer challenge with enterotoxigenic Escherichia coli (ETEC) has been used for four decades to elucidate the pathogenesis and immune responses and assess efficacy of various interventions. We performed a systematic review of these studies and a meta-analysis of individual patient-level data (IPD) from a subset of studies using standard methodology.

We identified 27 studies of 11 ETEC strains administered to 443 naive subjects at doses from 1 × 10⁶ to 1 × 10¹⁰ colony forming units (cfu). Diarrhea attack rates varied by strain, dose and enterotoxin. Similar rates were seen at doses of 5 × 10⁸ to …

Safety And Immunogenicity Of An Intranasal Shigella Flexneri 2a Invaplex 50 Vaccine, Mark S. Riddle, Robert W. Kaminski, Carlos Williams, Chad Porter, Shahida Baqar, Alexis Kordis, Theron Gilliland, Joyce Lapa, Melissa Coughlin, Chris Soltis, Erica Jones, Jackie Saunders, Paul B. Keiser, Ryan T. Ranallo, Robert Gormley, Michael Nelson, K. Ross Turbyfill, David Tribble, Edwin V. Oaks

Uniformed Services University of the Health Sciences

Background: Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device.

Methods: Volunteers (N = 36) were randomized to receive vaccine via the Dolphin^TM (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N = 8) received the 240 μg dose via pipette. Vaccine safety was …