New serotypes of Morganella morganii.

On the basis of 8 new O and 11 new H antigens determined in 22 strains, the Morganella morganii antigenic schema was supplemented with 8 serogroups (O35-O42) and 13 serotypes. Four strains belonged to O groups described earlier and 2 strains contained new O antigens in combination with known O antigens. Known H antigens were present in one strain as a single factor and in one strain as combination of two factors. New H antigens were demonstrated in 5 serotypes in combination with known H antigens. Six out of the 22 isolates were classified into O group 35. Two isolates contained different B-type surface antigens; these factors were not related to Escherichia coli B antigens and, unlike the latter, their living suspension gave a higher titre agglutination in OK serum as compared to the boild culture.     

Antigenic characteristics of standard strains of Providencia rettgeri (O- and H-antigens)

Additions and changes have been introduced into the existing antigenic diagnostic scheme of P. rettgeri on the basis of the study of the antigenic structure of standard strains from foreign collections: new, formerly unknown varieties of somatic and flagellar antigens (O35, O36, H27, H28) have been discovered, the complex of antigenic factors for H-antigens 7, 10, 23, 27 has been discovered. Strains 958 (36 : 28) and 979 (16 : 27a, 23b, 2a), previously classified with the genus Morganella, have been identified by O- and H-antigens.     

Antigenic relationship between Morganella morganii and Yersinia enterocolitica.

Two new O antigens have been described for the Morganella morganii antigenic schema. O antigens of the strains representing the new serotypes (O43 :H2 and O44 : H19, 37) are related to Yersinia enterocolitica O9 and O17, respectively.     

Water-soluble proteins in early amphibian embryos. III. Immunoelectrophoretic analysis of the antigenic changes in the ectoderm of the early gastrula and neural plate during development

20 water-soluble antigen have been identified with the help of rabbit antisera to extracts of the early gastrula ectoderm and neural plate in Rana temporaria. All of them were also found in the early blastula embryos and unfertilized eggs. The identified antigens are characterized by a definite embryospecificity. As the development proceeds, the concentration of these antigens in the embryonic tissues decreases until the complete disappearance of corresponding immunoelectrophoretic reactions. By this characteristic all antigens under study are subdivided into four groups: I--five antigens identified at the early developmental stages only (until hatching, stage 29); II--nine antigens present up to stages 33--35; III--three antigens followed up to stages 39--40 (well formed tadpole); IV--three antigens were found at all developmental stages under study up to stages 45--47. 11 out of 20 identified antigens have antigenic similarity with the proteins of blood serum of adult amphibians. Besides, the early gastrula ectoderm contains antigens similar with those of the brain of adult amphibians.     

New O and H antigens of the international antigenic scheme forPlesiomonas shigelloides

A revised update of the International antigenic scheme forPlesiomonas shigelloides is presented. Twenty-six new O (O77–O102) and 10 new H (H42–H50 and H1a1d) antigens have been described since 1994. The sources of antigens are mostly human clinical strains, isolates from warmblooded animals and a few environmental cultures.     

Intergeneric antigenic relation of Hafnia and Shigella (S. flexneri and S. boydii) bacteria

The O-antigenic relationships between Hafnia and Shigellae (S. flexneri and S. boydii) have been studied. For the first time the presence of antigenic relationship between Hafnia O19, O4, O9, O33, O5, O16, O12, O7, O29, O28, O10, O32, O24, O25, O18, O1, O13, O3, O22, O30, O37, O14, O11, O25, O23, O21, O28, O16, O24, O8, O26, O27 and S. flexneri la, lb, 2a, 2b, 4a, 4b, 6, 5a, 5b, as well as between Hafnia O10, O21, O35, O36, O9, O28, O8, O30 and S. boydii 1, 3, 6, 14, 2, 5, 2, 12 have been revealed. The character and degree of manifestation of antigenic relationships between the above-mentioned groups of bacteria have been established.     

On the serology of Plesiomonas shigelloides

The serology of 87 strains of Plesiomonas shigelloides was studied. Thirty O antigenic groups and 11 H antigens were defined within the 87 strains, and an antigenic schema consisting of 40 serovars was established. Some O antigens of P. shigelloides were identical or closely related to those of some Shigella serovars.     

Elevation in Plasma Abeta42 in Geriatric Depression: A Pilot Study

Elevated plasma amyloid beta 1–42 (Aβ42) level has been linked to increased risk for incident AD in cognitively-intact elderly. However, plasma Aβ levels in individuals with late-life depression (LLMD), especially those with a late age of onset of first depressive episode, who are at a particularly increased risk for Alzheimer’s disease, have not been studied. We compared plasma Aβ in 47 elderly with LLMD with 35 controls and examined its relationships to age of onset of first depressive episode, antidepressant treatment (paroxetine or nortriptyline), and indices of platelet activation (platelet factor 4 and beta-thromboglobulin) and brain abnormalities. Results indicated that plasma Aβ42 levels and the Aβ42/40 ratio were elevated in the LLMD group relative to controls in the overall group analyses and in the age- and gender-matched groups. MRI data indicated that higher Aβ42/40 ratio was associated with greater severity of total white matter hyperintensity burden in LLMD. Plasma Aβ levels in LLMD were not influenced by age of onset of first depressive episode or antidepressant treatment and were not related to indices of platelet activation. Our preliminary results suggest that increased plasma Aβ42 and Aβ42/40 ratio are present in geriatric depression, and future studies should be done to confirm these findings and to determine their relationship to cognitive decline and brain abnormalities associated with LLMD.Presented at the 43rd Annual Meeting, American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 12–16, 2004.     

Molecular Evolution of the Human Enteroviruses: Correlation of Serotype with VP1 Sequence and Application to Picornavirus Classification

Sixty-six human enterovirus serotypes have been identified by serum neutralization, but the molecular determinants of the serotypes are unknown. Since the picornavirus VP1 protein contains a number of neutralization domains, we hypothesized that the VP1 sequence should correspond with neutralization (serotype) and, hence, with phylogenetic lineage. To test this hypothesis and to analyze the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 sequences of the prototype strains of 47 human enterovirus serotypes and 10 antigenic variants. Our sequences, together with those available from GenBank, comprise a database of complete VP1 sequences for all 66 human enterovirus serotypes plus additional strains of seven serotypes. Phylogenetic trees constructed from complete VP1 sequences produced the same four major clusters as published trees based on partial VP2 sequences; in contrast to the VP2 trees, however, in the VP1 trees strains of the same serotype were always monophyletic. In pairwise comparisons of complete VP1 sequences, enteroviruses of the same serotype were clearly distinguished from those of heterologous serotypes, and the limits of intraserotypic divergence appeared to be about 25% nucleotide sequence difference or 12% amino acid sequence difference. Pairwise comparisons suggested that coxsackie A11 and A15 viruses should be classified as strains of the same serotype, as should coxsackie A13 and A18 viruses. Pairwise identity scores also distinguished between enteroviruses of different clusters and enteroviruses from picornaviruses of different genera. The data suggest that VP1 sequence comparisons may be valuable in enterovirus typing and in picornavirus taxonomy by assisting in the genus assignment of unclassified picornaviruses.Human enteroviruses (family Picornaviridae) infect millions of people worldwide each year, resulting in a wide range of clinical outcomes ranging from inapparent infection to mild respiratory illness (common cold), hand-foot-and-mouth disease, acute hemorrhagic conjunctivitis, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, and acute flaccid paralysis (reviewed in references 43 and 45). In the United States, enteroviruses are responsible for 30,000 to 50,000 meningitis hospitalizations per year as a result of 30 million to 50 million infections. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of an antibody neutralization test (43), and additional antigenic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between prototype and variant strains (6, 8, 68, 71, 72). On the basis of their pathogenesis in humans and experimental animals, the enteroviruses were originally classified into four groups, polioviruses, coxsackie A viruses (CA), coxsackie B viruses (CB), and echoviruses, but it was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups (8). The more recently isolated enteroviruses have been named with a system of consecutive numbers: EV68, EV69, EV70, and EV71 (42).A comparison of nucleotide and deduced amino acid sequences at the 5′ end of VP2 has identified four major phylogenetic groups within the Enterovirus genus: CA16-like viruses (cluster A), a CB-like group containing all CB and echoviruses as well as CA9 and EV69 (cluster B), poliovirus-like viruses (cluster C), and EV68 and EV70 (cluster D) (23, 24, 49, 53, 54, 73). However, pairwise alignments and phylogenetic analyses within these groups demonstrated that the VP2 sequence does not fully correlate with serotype, as viruses known to belong to the same serotype often failed to cluster together (2, 49). (E22 and E23 are genetically distinct from enteroviruses [24], and their reclassification into a separate genus has been proposed [45]).VP1 is the most external and immunodominant of the picornavirus capsid proteins (58). A number of major neutralization sites reside in the VP1 proteins of many picornaviruses (reviewed in references 40 and 44), but the specific epitopes responsible for serotype specificity and intratypic variation have not been identified. Similarly, the genetic correlates of serotype identity remain unknown. If the important serotype-specific neutralization sites reside in VP1, then the VP1 sequence or some portion thereof would be predicted to correlate with serotype. Studies on the three serotypes of poliovirus have shown that a partial VP1 sequence correlates well with serotype (32). In addition, genetic lineages based on the VP1 sequence can be used to define poliovirus reservoirs and chains of transmission (reviewed in reference 30). To test whether the VP1 sequence might be applied to the classification of nonpolio enteroviruses and to the analysis of the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 nucleotide sequences for 47 human enterovirus prototypes and 10 well-characterized antigenic variants. These data, together with previously available sequences, comprise a database of complete VP1 sequences for all known human enterovirus serotypes and 12 natural antigenic variants. This database will be useful for molecular epidemiologic studies of enteroviral disease outbreaks, to obtain a better understanding of the genetic correlates of serotype, and for the development of enteroviral molecular diagnostic reagents.     

Chimeric polioviruses that include sequences derived from two independent antigenic sites of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies against FMDV in guinea pigs.

Five poliovirus recombinants containing sequences corresponding to foot-and-mouth disease virus (FMDV) antigenic sites were constructed. Viable virus was recovered from four of these plasmids, in which the VP1 beta B-beta C loop (antigenic site 1) of poliovirus type 1 Sabin had been replaced with sequences derived from the VP1 beta G-beta H loop (antigenic site 1) of FMDV O1 Kaufbeuren (O1K), chimera O1.1 (residues 141 to 154), chimera O1.2 (residues 147 to 156), and chimera O1.3 (residues 140 to 160) or from the beta B-beta C loop of VP1 (antigenic site 3) in chimera O3.1 (residues 40 to 49). One chimera (O1.3) was neutralized by FMDV-specific polyclonal serum and monoclonal antibodies directed against antigenic site 1 of FMDV. Chimeras O1.3 and O3.1 induced site-specific FMDV-neutralizing antibodies in guinea pigs. Chimera O1.3 was capable of inducing a protective response against FMDV challenge in some guinea pigs.     

Immunochemical characterization of the outer membrane complex of Serratia marcescens and identification of the antigens accessible to antibodies on the cell surface

Serratia marcescens New CDC O14:H12 contains major outer membrane proteins of 43.5 kDal, 42 kDal (the porins) and 38 kDal (the OmpA protein) which can be separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Immunoblotting of whole cell or outer membrane preparations using antiserum raised against the whole cells revealed similar complex patterns of antigens. The OmpA protein was the major immunogen, although six other outer membrane proteins were also detected; the porins reacted only weakly with antibodies in this system. Immunoabsorption of antisera with whole cells showed that only the O antigenic chains of lipopolysaccharide and the H (flagella) antigens were accessible to antibody on the cell surface. Failure to detect the OmpA protein and other envelope antigens in this way suggests that their antigenic sites are not able to react with antibodies and are possibly masked by the O antigen.     

Shared and non-shared antigens from three different extracts of the metacestode of Echinococcus granulosus

Hydatid cyst fluid (HCF), somatic antigens (S-Ag) and excretory-secretory products (ES-Ag) of Echinococcus granulosus protoscoleces are used as the main antigenic sources for immunodiagnosis of human and dog echinococcosis. In order to determine their non-shared as well as their shared antigenic components, these extracts were studied by ELISA-inhibition and immunoblot-inhibition. Assays were carried out using homologous rabbit polyclonal antisera, human sera from individuals with surgically confirmed hydatidosis, and sera from dogs naturally infected with E. granulosus. High levels of cross-reactivity were observed for all antigenic extracts, but especially for ES-Ag and S-Ag. Canine antibodies evidenced lesser avidity for their specific antigens than antibodies from human origin. The major antigenic components shared by HCF, S-Ag, and ES-Ag have apparent molecular masses of 4-6, 20-24, 52, 80, and 100-104 kDa, including doublets of 41/45, 54/57, and 65/68 kDa. Non-shared polypeptides of each antigenic extract of E. granulosus were identified, having apparent masses of 108 and 78 kDa for HCF, of 124, 94, 83, and 75 kDa for S-Ag, and of 89, 66, 42, 39, 37, and 35 kDa for ES-Ag.     

The HLA system of the Uzbek population in the Ferghana Valley. HLA antigens, genes and haplotypes of the Uzbek population in relation to its ethnogenesis

Pecularities of distribution of 40 HLA antigens within the Uzbek population of the Ferghana Valley have been studied. The frequencies of these antigens are subdivided into three main groups having frequencies characteristic of the following populations: Caucasoid population (A9, B40, Bw22 etc.); Mongoloid population (B8, B7, B12); Middle Asian population (Aw31, B13, B16, Bw35), probably. The Uzbek population contains haplotypes both of Europeoid (Aw30, B13; A3, Bw35) and Mongoloid origin (A9, B40) and, probably, of the local origin (A1, B14; A1, Bw53; Aw32, B40). The data on the HLA genetics of the Uzbeks confirm the historical, linguistic and anthropological information concerning the role of inhabitants of the Central Asia in ethnogenesis and formation of the modern Uzbek population.     

Trichinella spiralis: strong antibody response to a 49 kDa newborn larva antigen in infected rats

In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000 muscle larvae (ML) and bled at different time intervals up to day 31 post infection (p.i.). Ab production was higher with 2000 ML dose and decreased with 8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on day 19 and remained high until the end of the study. Abs bound strongly at least to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97 kDa (described previously as TSL-1 antigens) occurred late in the infection. A follow-up of antigen recognition up to day 61 with the optimal immunization dose (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days p.i., which suggested antigenic differences with the previously reported 43 kDa ML antigen strongly recognized late in the infection. To analyze the stage-specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa NBL component in NBL total soluble extract but no reactivity was observed with soluble antigen of the other T. spiralis stages. Albeit with less intensity, the 49 kDa component was also recognized by PoAb together with other antigens of 53, 97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results reveal differences in the kinetics of anti-NBL and ML Ab responses. While anti-NBL Abs declined slowly from day 19 until the end of the experiment, Abs to ML antigen remained high in the same period. It is remarkable the optimal Ab response to NBL antigens with 2000 ML infective dose and the reduced number of NBL antigens identified throughout the experimental T. spiralis infection, standing out the immunodominant 49 kDa antigen. Interestingly, this antigen, which was prominently expressed in NBL somatic proteins, was also detected in NBL-ESP.     

Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5

The human class II, HLA-linked, B cell alloantigens include the HLA-DR, MB, MT, and Te determinants. Interest in the molecular relationships of these antigens has recently intensified because of their homology to the murine Ia antigens and their possible importance in disease predisposition and transplantation. We have used alloantisera with carefully defined immunochemical as well as serologic specificity, and two immunochemical techniques, sequential immunoprecipitation with analysis by SDS-PAGE and two-dimensional gel electrophoresis, to explore the molecular relationships of the MT2, MB3, MT4, and HLA-DR5 antigenic determinants. The data presented here indicate that 1) all class II molecules that bear the DR5 antigenic determinant also bear the MT2 antigenic determinant; (2) the homozygous DR5 cell line, Swei, expresses at least two structurally distinct class II molecules, both of which bear MT2: one bears the MT2, MB3, and MT4 antigenic determinants, and the second bears the MT2, but not the MB3 or MT4 antigenic determinant; and (3) the DR5 determinant is located on at least one and possibly both of these distinct class II molecules.     

Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: an immunocytological study in the central nervous system

Four monoclonal antibodies are characterized that have been obtained from a fusion of mouse myeloma P3-NS1/1-Ag4-1 with spleen cells from BALB/c mice immunized with white matter from bovine corpus callosum. The corresponding antigens (O antigens) are designated O1, O2, O3, and O4. The localization of these antigens was investigated by indirect immunofluorescence in cultures of early postnatal mouse cerebellum, cerebrum, spinal cord, optic nerve, and retina. When tested on live cultures none of the O antibodies reacted with the surface of astrocytes, neurons, or fibroblasts, however, all are positive on the surface of oligodendrocytes. The identity of these cells was determined by double-immunolabeling experiments with indpendent cell-type-specific antigenic markers (glial fibrillary acidic protein, tetanus toxin receptors, fibronectin, and galactocerebroside). Antigen O1 is exclusively expressed on galactocerebroside-positive cells, whereas O2, O3, and O4 are expressed on additional cells that are negative for any of the markers tested. None of the O antigens is expressed on the surface of cultured retinal cells. In fresh-frozen sections of adult mouse cerebellum all O antigens are detectable in white matter tracts and in vesicular structures of the granular layer. O2 and O3 antigens are in addition detectable in GFA protein-positive radial fibers in the molecular layer. In fixed cerebellar cultures, where intracellular antigens are accessible, O1, O2, and O3 antibodies label astrocytes in a GFA protein-like pattern. O antigens are expressed in mouse, rat, chicken, and human central nervous systems. O antibodies belong to the IgM immunoglobulin subclass and have been used in complement-dependent cytotoxic elimination of cerebellar oligodendrocytes in culture. At limiting antibody dilutions all processes of oligodendrocytes are preferably lysed over cell bodies.     

Analysis of excretory-secretory and somatic antigens of Gastrothylax crumenifer

The excretory/secretory (ES) metabolic products released by Gastrothylax crumenifer (Trematoda: Digenea) during in vitro incubations and the somatic extract of the adult parasite were analysed using polyacrylamide gel electrophoresis (PAGE). Immunogenicity of ES and somatic extracts were evaluated by immunoblotting and ELISA using sera raised against ES and somatic antigens in rabbits. The electropherograms of ES and somatic extracts have been resolved into 38 and 41 polypeptides, respectively. The apparent molecular weights of these polypeptides range from < 29 to > 205 kDa. A total of 14 polypeptides were found to be common to both of the samples. The analysis of immunoblot results revealed 22 and 27 antigenic polypeptides in ES and somatic extracts respectively. Only 11 and 13 antigenic polypeptides were found specific to ES and tissue extract respectively. The molecular weights of these specific polypeptides were calculated to be < 14.4, 16, 20, 25, 33, 42, 119, 125 and > 205 kDa for metabolic products and < 14.4, 25, 30, 35, 78, 84 and > 205 kDa for the tissue extracts, respectively. Analysis of ELISA results revealed that a dilution of up to 1:3200 of the test sera could react with the ES product. Further, when the ES antigens were allowed to react with antisomatic extracts in hyperimmune sera the titre of IgG increased up to a dilution of 1:12800. The potential importance of these antigens in the immunodiagnosis of amphistomiasis is discussed.     

Quantifying Antigenic Relationships among the Lyssaviruses

All lyssaviruses cause fatal encephalitis in mammals. There is sufficient antigenic variation within the genus to cause variable vaccine efficacy, but this variation is difficult to characterize quantitatively: sequence analysis cannot yet provide detailed antigenic information, and antigenic neutralization data have been refractory to high-resolution robust interpretation. Here, we address these issues by using state-of-the-art antigenic analyses to generate a high-resolution antigenic map of a global panel of 25 lyssaviruses. We compared the calculated antigenic distances with viral glycoprotein ectodomain sequence data. Although 67% of antigenic variation was predictable from the glycoprotein amino acid sequence, there are in some cases substantial differences between genetic and antigenic distances, thus highlighting the risk of inferring antigenic relationships solely from sequence data at this time. These differences included epidemiologically important antigenic differences between vaccine strains and wild-type rabies viruses. Further, we quantitatively assessed the antigenic relationships measured by using rabbit, mouse, and human sera, validating the use of nonhuman experimental animals as a model for determining antigenic variation in humans. The use of passive immune globulin is a crucial component of rabies postexposure prophylaxis, and here we also show that it is possible to predict the reactivity of immune globulin against divergent lyssaviruses.Rabies remains a globally important zoonosis, despite being one of the oldest recognized infectious diseases (27, 55). The majority of rabies in terrestrial animals and humans is caused by classical rabies virus (RABV), a lyssavirus in the family Rhabdoviridae. Since the 1950s, many related lyssaviruses which are capable of causing clinical rabies have been identified. The majority of those viruses have been isolated from bats (Chiroptera), including four divergent viruses, which were isolated in separate geographic locations throughout Eurasia in the past 18 years (2, 29, 31). The Chiroptera, therefore, represent a global reservoir for lyssaviruses, creating the potential for “spillover” infection to terrestrial mammals, including humans. Occasionally transmission between members of a new host species will occur, with potential for a subsequent adaptation in that species (35). Phylogenetic evidence suggests that one or more host-switching events from bats into terrestrial mammals were originally responsible for the ongoing global epidemic of terrestrial RABV (6).Pre- or postexposure prophylaxis, using vaccination and passive immune globulin administration according to World Health Organization (WHO) guidelines, is currently the only effective way to prevent rabies after infection with a lyssavirus (1). The efficacy of both active and passive immunization is likely to be affected by antigenic differences between viruses. The lyssavirus trimeric glycoprotein is the primary surface antigen, the major target for neutralizing antibodies (8), and is involved in cell binding and entry (34, 36, 53). Antigenic sites on the glycoprotein have been described using monoclonal antibody escape mutants (8, 16, 47, 51). These studies have elucidated two major sites (sites II and III) and multiple minor sites. Although estimates of antigenic differences can be made using information regarding these known antigenic sites, protein structure, and amino acid properties, predictions of the relative importance of those sites and specific mutations within those sites cannot be quantitatively tested without a method to reliably measure antigenic effect.The use of serological cross neutralization data to measure antigenic difference is limited by the reliability of the serological test and, more importantly, by paradoxes, or irregularities in the data. These irregularities include higher heterologous than homologous titers and individual variations between sera raised against the same antigen (22, 52). Hence, serological data are considered to have low resolution, and they are often used only qualitatively. Despite these difficulties, studies have attempted to further quantify antigenic differences among lyssaviruses. Badrane et al. (5) showed a linear correlation between the glycoprotein amino acid identity and four cross neutralization titers. Other studies have demonstrated variable serological cross-reactivity between European bat lyssaviruses (EBLV) and RABVs (10, 11) and suggested that antigenic relationships between EBLV-1 and EBLV-2 may not be fully reflected in the genetic relationships (41). Recent investigations into the efficacy of biologics against the Eurasian lyssaviruses showed an array of relatedness between lyssavirus species, with, for example, a murine anti-Aravan virus (anti-ARAV) serum neutralizing Khujand virus (KHUV) and ARAV equally but an anti-KHUV serum being less effective at neutralizing ARAV than KHUV (22). Until recently, however, there were no established tools for the quantitative analysis of antigenic data.Here we resolve the issue of quantitative interpretation of antigenic data using antigenic cartography. Antigenic cartography is a theory and associated computational method that resolves the paradoxes in the interpretation of antigenic data and makes possible high-resolution quantitative analyses and visualizations of binding assay data (15, 20, 25, 44, 49, 52).Integrating antigenic data with direct sequencing data, here we quantify the antigenic and genetic variation among a global panel of lyssaviruses, including representatives from all lyssavirus species. Furthermore, we address two key issues in the development of antilyssavirus biologics: the appropriateness of animal models and the development of efficacious alternatives to human rabies immune globulins (HRIGs).     

Influence of phase I duration on phase II VO2 kinetics parameter estimates in older and young adults

Older adults (O) may have a longer phase I pulmonary O(2) uptake kinetics (Vo(2)(p)) than young adults (Y); this may affect parameter estimates of phase II Vo(2)(p). Therefore, we sought to: 1) experimentally estimate the duration of phase I Vo(2)(p) (EE phase I) in O and Y subjects during moderate-intensity exercise transitions; 2) examine the effects of selected phase I durations (i.e., different start times for modeling phase II) on parameter estimates of the phase II Vo(2)(p) response; and 3) thereby determine whether slower phase II kinetics in O subjects represent a physiological difference or a by-product of fitting strategy. Vo(2)(p) was measured breath-by-breath in 19 O (68 ± 6 yr; mean ± SD) and 19 Y (24 ± 5 yr) using a volume turbine and mass spectrometer. Phase I Vo(2)(p) was longer in O (31 ± 4 s) than Y (20 ± 7 s) (P < 0.05). In O, phase II τVo(2)(p) was larger (P < 0.05) when fitting started at 15 s (49 ± 12 s) compared with fits starting at the individual EE phase I (43 ± 12 s), 25 s (42 ± 10 s), 35 s (42 ± 12 s), and 45 s (45 ± 15 s). In Y, τVo(2)(p) was not affected by the time at which phase II Vo(2)(p) fitting started (τVo(2)(p) = 31 ± 7 s, 29 ± 9 s, 30 ± 10 s, 32 ± 11 s, and 30 ± 8 s for fittings starting at 15 s, 25 s, 35 s, 45 s, and EE phase I, respectively). Fitting from EE phase I, 25 s, or 35 s resulted in the smallest CI τVo(2)(p) in both O and Y. Thus, fitting phase II Vo(2)(p) from (but not constrained to) 25 s or 35 s provides consistent estimates of Vo(2)(p) kinetics parameters in Y and O, despite the longer phase I Vo(2)(p) in O.     

Antigenic and cross-protection studies of biotype 1 and biotype 2 isolates of Yersinia ruckeri in rainbow trout, Oncorhynchus mykiss (Walbaum)

Aims: The study investigated antigen characteristics of biotype (bt) 1 and bt 2 isolates of Yersinia ruckeri. Methods and Results: The cell surface characteristics of Y. ruckeri were compared for their antigenic characteristics using polyclonal antibodies that revealed that both biotypes had a homogenous whole‐cell protein antigenic profile. Notable differences in the antigenic properties were observed in the lipopolysaccharide profile of both biotypes. Two iron‐regulated outer membrane proteins (IROMP) of c. 90 and 100 kDa were shown to be major specific antigens. The results demonstrate for the first time differences in antigens between bt 1 and bt 2 isolates of serotype O1 isolates of Y. ruckeri. The protection induced in rainbow trout by a commercial monovalent, and bivalent inactivated vaccine was tested with the outcome that the ability of isolates to cause mortality in vaccinated fish varied with geographical location. In this context, vaccination studies suggested that the O antigen was the dominant immunogenic molecule involved in protection against the disease. Conclusions: The O antigen of Y. ruckeri was the dominant immunogenic molecule involved in the protection of rainbow trout against enteric redmouth disease. Significance and Impact of the Study: There are distinct phenotypic and antigenic differences in Y. ruckeri bt 1 and bt 2 with O antigen recognized as the dominant immunogenic molecule. The data have significance in explaining the lack of success of the earlier monovalent vaccine and demonstrate the effectiveness of the newer bivalent vaccine.