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[The 2003/2004 influenza season in the Netherlands with a limited epidemic of the virus variant A/Fujian, and the vaccine composition for the 2004/2005 season].

In contrast to the three previous influenza seasons, the influenza epidemic of the 2003/2004 season started early in week 49 of 2003. The epidemic was predominantly caused by influenza-A viruses of the H3N2 subtype. All isolated influenza-A viruses were antigenically related to influenza virus A/Fujian/411/02, which was already detected in the influenza season 2002/2003 and that deviated from the vaccine-reference strain A/Moscow/10/99 to a certain extent. The magnitude of the epidemic was limited despite the fact that it was caused by influenza-A H3N2-virus-drift variants. Immunity caused by natural infection with influenza viruses during previous seasons or vaccination has possibly provided sufficient cross protection against these new H3N2-drift variant. No influenza-A viruses of the H1N1 or H1N2 subtypes were detected in the influenza season 2003/2004. Only a small number of influenza-B viruses were isolated, which all belonged to the B/Yamagata/16/88 lineage, which was temporarily replaced by the B/Victoria2/87 lineage in the previous influenza season. On the basis of epidemiological and serological data the World Health Organization has recommended the following vaccine composition for the 2004/2005 influenza season: A/Fujian/411/02 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Shanghai/361/02.

Global Health↗

Antigenic variation among strains of Eimeria maxima and E. tenella of the chicken.

The immunogenicity and cross-protection of Eimeria maxima or E. tenella in chickens against their homologous and heterologous strains were evaluated in two experiments. The immunizing strain of E. tenella protected against itself and partially against heterologous strains. The North Carolina (NC) strains of E. tenella were more virulent than the Delmarva (DMV) strains. Growth of the unimmunized groups was depressed 66% and 32% for the NC and DMV strains, respectively. Growth of the immunized-challenged groups (DMV and NC) was depressed by 13%. The DMV E. maxima strains were more virulent than the NC strains. Growth of the unimmunized challenged groups was depressed by 47% (DMV) and 13% (NC). Results demonstrated that there are antigenic variations among strains of two species of chicken coccidia.

Animals↗

[Comparative study of immunobiological properties of Klebsiella planticola and Klebsiella pneumoniae strains].

The present investigation was based on information on the frequent isolation of K. planticola, inhabiting soil and water ecosystems, from respiratory tract secretions, urine, wound surface and other clinical material in infectious pathology of humans. The comparative study of the main immunobiological properties of K. planticola strain TCXA 91 and K. pneumoniae strain 204 was carried out. The strains were equally virulent for white mice, the infective dose being about 100x10(6) when introduced intraperitoneally in 0.4% agar. These strains exhibited protective cross activity in the animals challenged with K. pneumoniae virulent strain K16. The survival rates of mice for K. planticola TCXA 91 and K. pneumoniae 204 were, respectively, 60% and 70%, the death rate of the control animals being 100%. For the first time K. pneumoniae 204 was found capable of stimulating the growth of lawn grasses in the presence of sodium chloride. The results were evaluated by the germination of seeds, the length of the plantlet and the root. The data obtained in this study are indicative of the similarity of the immunobiological properties of K. planticola TCXA 91 and K. pneumoniae 204.

Animals↗

[Genetic mutations of heamagglutinin genes of H9N2 subtype influenza A viruses in the field in a five-year period].

Infection in chicken flocks on a farm, where AI outbreak took place in 1998, was monitored in a four-year consecutive period and 22 H9N2 subtype viruses were isolated. The HA gene and antigenicity of 9 strains among isolates were compared with that of isolate of 1998. The results indicated that mutations of HA genes of H9 subtype influenza A viruses were observed during five years. However these mutations of HA genes didn't lead to sufficient antigenic variation to change the cross-protective pattern of these strains. These findings may be fruitful for making further study of genetic mutations of AIVs in the field and improving the control strategies.

Animals↗

Leptospirosis vaccines: past, present, and future.

It is well known that Leptospira vaccine prevents the disease. However specificity for serovars limits the efficacy of killed whole cell vaccines. Leptospiral antigens that induce cross-protective immunity to the various serovars are sought as new vaccine candidates. In this paper, we have summarized both past and current findings about leptospiral antigens that are conserved among pathogenic leptospires and that induce protective immunity in animal models. The full-length genome sequences of two Leptospira strains have been published and reverse vaccinology has been used to identify leptospiral vaccine candidates. Although humoral immunity is thought to be dominant in protection from leptospiral infection, a role for cell-mediated immunity is now being explored.

Antigens, Bacterial↗

Hypoxia and resistance to hydrogen peroxide confer resistance to tumor necrosis factor in murine L929 cells.

The mechanism whereby tumor necrosis factor (TNF) kills mammalian cells is not well understood, although oxidative damage has been suggested by several investigators. Further, it is not known why cells vary in their responsiveness to TNF. We show that the cytotoxic effect of TNF toward TNF-sensitive L929 cells is blocked under hypoxic conditions, suggesting a critical role of molecular oxygen and reactive oxygen species. To test whether cellular resistance to reactive oxygen species could provide resistance to TNF, we derived a variant strain from L929 cells by chronic exposure to an oxidizing agent, hydrogen peroxide (H2O2). These cells exhibit marked resistance to TNF as well as to H2O2. This cross-protection provides additional evidence that mechanisms of resistance to oxidative damage are causally related to TNF-induced cell death. Scatchard analysis of TNF binding did not reveal significant differences between the H2O2-resistant line and the wild-type L929 line. On the other hand, analyses of antioxidant enzymes and glutathione levels in cells of the wild-type and the H2O2-resistant lines revealed several potentially important differences. Before exposure to TNF, the H2O2-resistant variants have elevated catalase activity, decreased activity of total glutathione-S-transferase (GST), and similar superoxide dismutase (SOD) activities. Exposure to TNF led to alteration in CuZnSOD activity, and much more so in the variants than in the wild-type L929 cells. However, no significant change in MnSOD activities in cells of either cell line was observed. Total GST activity was not altered appreciably by TNF in either cell line, but Western analysis showed that the level of alpha GST isozyme was increased and mu GST isozyme decreased in the H2O2-resistant variants. Furthermore, alterations in total glutathione content were observed in both the control and the variant cells.

Animals↗

Antigenic relationships of common rhinovirus types from disabling upper respiratory illnesses.

The frequency of the common cold has been though to be due to the existence of more than 89 different serologic types of rhinoviruses. However, in the civilian and military population studied in this area from 1962 through 1970, types 1A, 1B, 2, 23, 29, 30 and 31 accounted for 81 percent of 487 rhinoviruses isolated from individuals with respiratory illnesses. Antigenic relationships between these types and others have been demonstrated by neutralization in WI-38 cell cultures and by immunodiffusion. Types 1A and 1b, 2 and 49, 23 and 30, 29 and 44 and others are related. With specific animal antisera, heterotypic antibody titers are minimal. However, following natural infection in man with one of these related types, antibody responses to the other was almost equal to the homotype and could predictably provide cross-protection. Even with inactive T13 rhinovirus vaccine in man, protective levels of neutralizing antibody to T41 were produced. It is clear that the rates of rhinovirus colds would be greatly increased if more than 89 immunologic distinct types actually existed. An effective vaccine could be easily prepared by selection of a few appropriate types, such as 1A, 2, 23, 29 and 31.

Adolescent↗

Immunogenicity of infectious bursal disease viruses in chickens.

Cross-protective properties of infectious bursal disease viruses (IBDVs) were studied. Viruses represented different subtypes of serotype 1, including recently isolated viruses (variants), and a serotype 2 virus. Chickens were vaccinated at 3 weeks of age with inactivated vaccines containing 10(5), 10(6), 10(7), or 10(8) mean tissue-culture infectious dose of a given virus and challenged 2 weeks later using either 10(2) or 10(3.5) mean embryo infectious dose (EID50) of either a standard virus or a variant serotype 1 virus. Protection was evaluated at 5 and 10 days post-challenge, based on gross and microscopic lesions, body weight, and bursa/body-weight ratios. The serotype 2 virus did not confer protection on birds challenged with the serotype 1 viruses. Vaccines made of variant viruses at the low doses protected chickens challenged with the high or low doses of either the standard or the variant viruses. Vaccines made of the standard or variant strains at low doses protected against high or low challenge doses of the standard strain. Vaccines made of the high dose of any of the standard strains protected chickens against the variant virus when the low challenge dose (10(2) EID50) was used, but not when the high challenge dose (10(3.5) EID50) was used. The lowest dose of the standard viruses vaccines required to confer protection against the variant virus varied depending on the strain. Results indicated that protection depended on the strain and dose of both the vaccine and challenge viruses and that the variant strains and standard strains share a common protective antigen(s).

Animals↗

The effect of acid adaptation conditions on heat resistance of Escherichia coli O157: H7.

The objective of this study was to determine the effect of acid adaptation conditions on heat resistance of E. coli O157: H7 932. E. coli O157: H7 was adapted to acid by exposing the cells to pH 4.5 (2h), pH 5.0 (1 h), and pH 5.5 (1 h) in tryptic soy broth. D and z values of the acid adapted and control cultures at 54 degrees C, 56 degrees C, and 58 degrees C were determined in E buffer. The heat resistance of E. coli O157: H7 increased significantly (p<0.05) after acid adaptation at pH 4.5 or pH 5.0. E. coli O157: H7 adapted to acid at pH 4.5 for 2 h had the highest D values at all temperatures tested (20.3-10.7-3.3 min) while D values of culture adapted to acid at pH 5.0 for 1 h were 18.2, 7.9, and 2.6 min at 54 degrees C, 56 degrees C and 58 degrees C, respectively. Heat resistance of culture adapted to acid at pH 5.5 for 1 h and the control culture was not significantly different (P<0.05). Culture adapted to acid at pH 4.5 had the highest z value (5.10 degrees C), whereas control culture had the lowest z value (4.33 degrees C). This study showed that the magnitude of heat tolerance changed with the adaptation pH and at low adaptation pH, E. coli O157: H7 showed maximum heat resistance. Acid adaptation at pH 4.5 or 5.0 provides E. coli O157: H7 with cross-protection against heat treatments, and that this factor must be considered to estimate this pathogen's thermal tolerance accurately.

Adaptation, Physiological↗

Selection of foot and mouth disease vaccine strains--a review.

The choice of the most appropriate strains of foot and mouth disease (FMD) virus vaccines to use in FMD control programmes and to store in vaccine antigen reserves is based on the matching of representative field isolates from outbreaks around the world to available vaccine strains. However, those involved in FMD control at a national level do not always give this work a high priority, while in countries without effective control of FMD there is little incentive to collect samples or to overcome the constraints on submission to international reference laboratories. In the short term, specific initiatives for targeted collection can provide samples on a periodic basis, but a long-term solution requires the development of FMD control measures. This must be underpinned by the strengthening of local Veterinary Services and laboratories, and by demand-driven provision of sufficient amounts of high-quality vaccine. Difficulties may be increased by commercial constraints on disclosure of the strains used for vaccine production and on the supply of reagents needed for matching tests. Vaccine matching tests are mainly based on in vitro methods - such as virus neutralisation, enzyme-linked immunosorbent assay with polyclonal antibodies and complement fixation - and are performed in a relatively small number of laboratories around the world. In addition to the difficulties of gathering representative field and vaccine strains, neither the reagents nor the methods used for vaccine matching are fully harmonised. Consequently, there is no strict equivalence in the results obtained. Alternative approaches using monoclonal antibody panels and/or viral capsid gene sequencing are being developed and could complement the currently employed serological tests. However, there is limited in vivo cross-protection information, more of which is essential for future validation of the vaccine matching methods. In response to the funding and leadership deficit for vaccine strain selection, a network of World Organisation for Animal Health (OIE) and Food and Agriculture Organization FMD reference laboratories has been established; this gives these laboratories the potential to strengthen the coordination of their work and reporting and thereby improve recommendations on vaccine strain selection.

Animals↗

[Diarrhea and vaccines: current developments].

Diarrhoea is a main concern for travellers, populations of developing countries and children. Causative pathogens are numerous. An efficient vaccine against cholera is available, also offering a 50% cross-protection against E. Coli enterotoxin (ETEC), however its efficacy is only 23% against all-causes traveller's diarrhoea. Rotavirus can be responsible for severe diarrhoea in infants but rarely causes traveller's diarrhoea. Two new vaccines being under development appear effective and well-tolerated but too expensive for developing countries which most need them. To date, the live oral Ty21a vaccine remains frequently prescribed in Switzerland, with limited indications and suboptimal efficacy. A new oral vaccine is under development.

Bacterial Vaccines↗

Neutralization of a transmissible gastroenteritis virus of swine by colostral antibodies elicited by intestine and cell culture-propagated virus.

Cross-protection studies of gilts exposed to 4 transmissible gastroenteritis viruses--Ilinois (field strain), Miller-3, Miller low passage (M-LP), and Miller high passage (M-HP) tissue culture-adapted--indicated that only the gilt vaccinated with Illinois strain was protected, along with its newborn pigs, against challenge exposure with field virus. Similar results were obtained when the 4 viruses were incubated in vitro with colostrum from each of the 4 vaccinated gilts and subsequently used to orally inoculate newborn pigs. However, when the colostrums were used to neutralize M-HP virus in cell cultures, the neutralization titers were similar, indicating that a close antigenic relationship existed among the viruses. Neutralization studies in cell cultures, using immunoglobulin (Ig) fractions derived from colostrums of sows exposed to Illinois and M-HP virus, indicated that Illinois virus elicited more neutralizing activity in IgA than in the IgG fraction and that M-HP virus elicited more IgG than IgA antibody activity. In another study, Illinois virus was treated with these Ig-enriched fractions and then inoculated into the lumen of the jejunum of 3-day-old pigs. Anti-Illinois IgA was the only class of antibody which prevented replication of the Illinois virus in the intestine. Similar intraintestinal inoculations were used to test invasiveness of untreated Illinois and M-HP viruses. It was demonstrated that Illinois virus caused marked effect on the intestine: shortening of the villi, intestinal distension, edema, and presence of accumulated intestinal fluid within 60 hours after inoculation. The M-HP virus grew in the intestinal cells without affecting the length of the villi. The degree of invasiveness of Illinois or M-HP virus may account for the difference in the antibody class elicited in the colostrums.

Animals↗

Variant serotypes of infectious bronchitis virus isolated from commercial layer and broiler chickens.

Twenty infectious bronchitis virus (IBV) field isolates obtained from commercial layer and broiler chickens in 1987 and 1988 were serotyped using the virus-neutralization (VN) test. Six different previously unrecognized variant serotypes were identified from a total of seven isolates from layer chickens. Only two isolates, both from Maine, were the same variant serotype. Variant serotypes also were recovered from layer flocks in Illinois and Washington and the province of Ontario, Canada. Two different variants were isolated from the same multi-age layer complex in Connecticut. Only one of 13 broiler chicken isolates was found to be a new variant serotype, that being from birds reared in Delaware. Cross-protection studies in specific-pathogen-free chickens indicated that vaccines containing the Holland, L-1, or Connaught strains of Massachusetts (Mass) combined with Arkansas produced a broader spectrum of immunity against challenge with the layer variants than Mass (Holland) alone or Mass (L-1) + Connecticut. All vaccines tested produced solid immunity (greater than or equal to 80% protection) against the broiler variant virus.

Animals↗

Tumor rejection antigens on BALB3T3 cells transformed by activated oncogenes.

The clonal expression of tumor rejection Ag (TRA) was analyzed on nine different clones derived from parental BALB3T3 cells that were transfected with activated H-ras, polyoma middle T (PyMT), c-myc, and v-src oncogenes. It was shown that Bras-h clone, which is an activated H-ras oncogene-induced transformant, expressed TRA as assessed in the transplantation study using syngeneic BALB/c mice. This TRA was not detected on parental BALB3T3 nontransformed cells, suggesting that TRA could be expressed in the BALB3T3 cell transformation. Furthermore, the cross-protection experiments indicated that this TRA was also conferred on other BALB3T3 transformants with high anchorage-independent growth potential such as an activated H-ras transformant Bras-d, and PyMT transformants BMT-f, BnMT-11, BnMT-20, except in the case of one H-ras transformant Bnr-12. In contrast, this TRA was not expressed on the transfectants with little or no anchorage independent growth potential such as a PyMT transfectant BnMT-4, a c-myc transfectant Bmyc-7, and a v-src transfectant Bsrc-7. We developed the mAb BRH19 that could react with TRA+ clones but not with TRA- clones. This mAb makes an immunoprecipitate, which is composed of a 50-kDa single polypeptide chain from Bras-h cell lysate. An injection to mice with this antigen could confer the protection against Bras-h challenge. These data indicate that the 50-kDa putative TRA molecule could be expressed in close association with the cell transformation, irrespective of the introduced oncogenes, and there may exist some regulatory mechanisms rather than individually distinct manners for the expression of TRA.

3T3 Cells↗

Anti-lipopolysaccharide antibodies in gram-negative bacteremia.

The experimental and clinical studies underlying the concept of cross-protection afforded by core lipopolysaccharides (LPS) antibodies are reviewed. These studies did not allow to clarify the epitope(s) and the effector mechanism(s) involved in the protection. Recently, two antilipid A IgM monoclonal antibodies, called E5 and HA-1A, have been investigated in patients with Gram-negative infections and a clinical picture of septicemia. E5 reduced the mortality of patients, bacteremic or not, but only as long as they were not in shock. A confirmatory study has been initiated. In contrast to E5, HA-1A protected patients in shock, but only when they were bacteremic at randomization. However, experimental studies have yielded contradictory results concerning the protective power of this antibody. Although the clinical studies suggest a beneficial effect of both antibodies in some patients, no definitive conclusions can be drawn until the extensive data will be published, and until further experimental investigations will have clarified the protective power of these antibodies.

Antibodies, Bacterial↗

Methods currently used for the control of Theileria annulata: their validity and proposals for future control strategies.

The development of a cell culture vaccine against tropical theileriosis in India is described. Observations on the experiments conducted for the standardization of dose, storage temperature, evaluation of immune response, cross-protection response and field immunization trials are summarized. Future strategies for epidemiological studies and the control of tropical theileriosis are discussed.

Animals↗

T cell tumor cure by T cell receptor-mediated activation requires the development of CD8-dependent host immunity.

The participation of the host in eliminating Ag-specific T hybridoma cells after their in vivo activation was studied. In our model system, treatment of the cytochrome c-specific T cell hybridoma 2B4.11 in vitro with Ag in the context of histocompatible APC results in cellular activation, as shown by IL-2 release and growth inhibition. In vivo treatment with Ag results in tumor cell elimination as a result both of a direct inhibitory effect of cytochrome c that is mediated through the 2B4.11 TCR and to the induction of host immunity. In vivo lymphocyte-depletion studies showed that CD8-bearing cells were critical to the successful elimination of tumor cells mediated by Ag, whereas depletion of CD4-bearing cells had only minor effects on the outcome. Cytotoxic cells from mice cured by Ag treatment lysed only 2B4.11 among a panel of related tumors, although in vivo cross-protection studies showed that 2B4.11-immune mice were also resistant to the growth of BW5147 and C10.9. Because spleen cells from 2B4.11 immune mice did not recognize 2B4.11 or other related tumors in proliferation assays, we concluded that a participant(s) with memory and specificity, not assayed in vitro, was also involved in the mediation of the immune effects observed. For therapies based on the use of less selective agents, i.e. mAb that share the activating properties of Ag but can react with T cell neoplasms of unknown specificity, it would appear that a relatively intact immune system is required for maximal success.

Animals↗

Antigenic variation in rabies virus strains.

Several rabies virus isolates from small wild rodents, one strain isolated from a fox and another from a cat, as well as the CVS strain were compared in cross-protection and virus-neutralization tests. Antigenic variations between the strains and between different batches of individual strains were found. These antigenic differences could not be explained by denaturation caused by UV irradiation or deep-freeze storage, by the presence of "incomplete" particles or by passage in immune organism. An antigenic difference was batch-specific and was only demonstrable on comparison with a relatively large number of strains: it has probably developed during the assembly of antigenic determinants of the virion. There was no correlation between protective and virus-neutralizing activities.

Animals↗