Clinical Evaluation of a Vaccinia-Vectored Hantaan Virus Vaccine

We evaluated a vaccinia-vectored vaccine for hemorrhagic fever with renal syndrome in clinical trials. A Phase I dose-escalation study in 16 volunteers divided into four groups demonstrated that subcutaneous inoculation of approximately 107 plaque-forming units of the recombinant virus was safe and immunogenic. Vaccination of a fifth group of 12 volunteers indicated that neutralizing antibody titers to both vaccinia virus and Hantaan virus were enhanced after a second inoculation. Comparing two routes of vaccination showed that scarification effectively induced neutralizing antibodies in vaccinia virus-naive volunteers but that subcutaneous inoculation was superior to scarification in vaccinia virus-immune individuals. A Phase II, double-blinded, placebo-controlled clinical trial was conducted among 142 volunteers. Two subcutaneous vaccinations were administered at 4-week intervals. Neutralizing antibodies to Hantaan virus or to vaccinia virus were detected in 72% or 98% of vaccinia virusnaive volunteers, respectively. In contrast, only 26% of the vaccinia virus-immune volunteers developed neutralizing antibody responses to Hantaan virus

Hantaviruses: a global disease problem.

Hantaviruses are carried by numerous rodent species throughout the world. In 1993, a previously unknown group of hantaviruses emerged in the United States as the cause of an acute respiratory disease now termed hantavirus pulmonary syndrome (HPS). Before than, hantaviruses were known as the etiologic agents of hemorrhagic fever with renal syndrome, a disease that occurs almost entirely in the Eastern Hemisphere. Since the discovery of the HPS-causing hantaviruses, intense investigation of the ecology and epidemiology of hantaviruses has led to the discovery of many other novel hantaviruses. Their ubiquity and potential for causing severe human illness make these viruses an important public health concern; we reviewed the distribution, ecology, disease potential, and genetic spectrum

Bacterial Expression of Neutralizing Mouse Monoclonal Antibody Fab Fragments to Hantaan Virus

AbstractWe amplified by polymerase chain reaction the heavy and light chain antibody genes of two mouse hybridomas secreting neutralizing monoclonal antibodies (MAbs) to the G1 or G2 envelope proteins of Hantaan virus, cloned them into the phagemid vector pComb3, and expressed them in bacteria to yield Fab fragments. Expressed Fab fragments had the same antigenic specificities for Hantaan and Seoul viruses as the complete parent MAbs and were able to neutralize Hantaan virus in plaque-reduction neutralization assays. The authentic MAb to G2 (HCO2) could passively protect hamsters from challenge with Hantaan virus when neutralizing antibody titers of at least 1:10 were detected in the animals’ sera just prior to challenge. In contrast, although 1:10 neutralization titers were also detected in hamsters receiving passively transferred,Escherichia coli-expressed HCO2 Fab, these animals were not protected from infection with Hantaan virus. Similarly, passive transfer of the HCO2 MAb on Days 1 through 4 after infection prevented antigen deposition in hamster lungs and kidneys but passive transfer of the recombinant HCO2 Fab did not. The results suggest that although neutralization by IgG antibodies correlates with protection in hamsters, the same may not be true for neutralizing Fab fragments

Smokejumper Magazine, April 2003

This issue of the National Smokejumper Association (NSA) Smokejumper Magazine contains the following articles: Tribute to Ed Guy (Dale Schmaljohn), FBI Join Probe into Ted Burgon Killing, Biscuit Fire – Initial Attack System Broken? (Chuck Sheley), Ration of Luck (Air America—Don Courtney), Remembering a Hero – Hugh Jenkins, Interview with Troop Emonds (Chris Sorensen), profiles Wally Henderson, Fred Donner and Jimmie Dollard. Smokejumper Magazine continues Static Line, which was the original title of the NSA quarterly magazine.https://dc.ewu.edu/smokejumper_mag/1038/thumbnail.jp

Thottapalayam Virus, a Prototype Shrewborne Hantavirus

This virus is antigenically and phylogenetically distinct from rodent-borne hantaviruses

Antigenicity and Vaccine Potential of Marburg Virus Glycoprotein Expressed by Baculovirus Recombinants

AbstractThere is no effective vaccine for Marburg virus (MBGV) or any other filovirus, nor enough pertinent information to expedite rational vaccine development. To ascertain some of the minimal requirements for a MBGV vaccine, we determined whether whole inactivated MBGV, or a baculovirus-expressed virion subunit, could be used to immunize guinea pigs against a lethal infection. Baculovirus recombinants were made to express the MBGV glycoprotein (GP) either as a full-length, cell-associated molecule or a slightly truncated (5.4%) product secreted into medium; the latter, for its far greater ease in manipulation, was tested for its vaccine potential. Like MBGV GP, both the full-length and truncated GP expressed by baculovirus recombinants were abundantly glycosylated with both N- and O-linked glycans; differences in glycosylation were detectable, but these could not be shown to affect antigenicity with respect to available antibodies. The recombinant truncated glycoprotein elicited protection against lethal challenge with the MBGV isolate from which it was constructed and less effectively against an antigenically disparate MBGV isolate. Killed (irradiated) MBGV antigen was protective, in a reciprocal fashion, against both MBGV types. In a preliminary assessment of possible protective mechanisms, serum antibodies from immune animals were shown to be sufficient for protecting naive guinea pigs from lethal MBGV infection

First Human Isolate of Hantavirus (Andes virus) in the Americas

We isolated Andes virus (formal name: Andes virus [ANDV], a species in the genus Hantavirus), from serum of an asymptomatic 10-year-old Chilean boy who died 6 days later of hantavirus pulmonary syndrome (HPS). The serum was obtained 12 days after his grandmother died from HPS and 2 days before he became febrile. No hantavirus immunoglobulin (Ig) G or IgM antibodies were detected in the serum sample. After three blind passages, ANDV antigens were detected in Vero E6 cells by immunofluorescence assay and enzyme-linked immunosorbent assay, and ANDV RNA was detected by reverse transcription-polymerase chain reaction. A fragment of the virus genome showed 96.2% nucleotide identity with that of prototype ANDV. To our knowledge, this is the first isolation of any agent of hemorrhagic fever with renal syndrome from a human and the first such isolation of hantavirus before symptoms of that syndrome or HPS began

Spatio-temporal patterns in the Hantavirus infection

We present a model of the infection of Hantavirus in deer mouse, Peromyscus maniculatus, based on biological observations of the system in the North American Southwest. The results of the analysis shed light on relevant observations of the biological system, such as the sporadical disappearance of the infection, and the existence of foci or ``refugia'' that perform as reservoirs of the virus when environmental conditions are less than optimal.Comment: 6 pages, 5 inlined figures, RevTeX 4 forma

Pathogenic Hantaviruses Elicit Different Immunoreactions in THP-1 Cells and Primary Monocytes and Induce Differentiation of Human Monocytes to Dendritic-Like Cells

Hantaviruses cause two important human illnesses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both syndromes are believed to be immune-mediated diseases. Monocytes/macrophages are thought to be the main target cells for hantaviruses and important sources of and targets for cytokines/chemokines secretion. THP-1 cells have been used extensively as models for primary monocytes in biocompatibility research. The aim of our study was to determine if hantaviruses induce the same immunoreactions in THP-1 cells and primary monocytes/ macrophages and might therefore be suitable for immune studies of hantaviral infections. For that purpose we compared various cytokines/chemokines and their receptors in THP-1 cell line and primary monocytes/macrophages. Infected primary monocytes/macrophages induced mostly -chemokines and their receptors. In contrast, THP-1 cells, expressed receptors for CXC chemokines. Surprisingly, infected macrophages underwent morphological changes toward dendriticlike cells and increased expression of co-stimulatory molecules: CD40, CD80, CD83 and CD86. Our data indicate that THP-1 cells are not ideal for in vitro research of the immunopathogenesis of hantaviruses in humans. Further, our studies revealed potential roles for cytokines/chemokines in HFRS/HPS immunopathogenesis and point to intriguing possibilities for the possible differentiation of infected macrophages to dendritic-like cells