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Prevalence of neutralizing antibodies against a candidate rotavirus vaccine in adults.

Because of the morbidity and mortality from infection with rotaviruses in children under 2 years, in many parts of the world but especially in developing countries, an urgent need for a vaccine has been recognized. At present, a vaccine candidate of bovine origin, the RIT 4237 strain vaccine developed from a strain received from Mebus et al., is available. This strain has been shown to induce cross protection by challenge of colostrum deprived piglets with human rotavirus strains. Before testing its protective effect in children, preliminary studies in adult volunteers are required to evaluate its degree attenuation and immunogenicity. With regard to the latter we have studied the antibody profile of 87 healthy adults, ages 25 to 40 years, from whom blood samples were taken between January and June 1982. Antibodies versus RIT 4237 were measured both by neutralization and ELISA techniques. Analysis of the results revealed a significant difference in antibody levels according to sex, since high neutralizing antibody titers (greater than 1:320) were observed about 7 times more frequently in women than in men. Furthermore, no seasonal variation in the level and the distribution of serum antibody titers was found when comparing blood specimens taken from male volunteers in winter and spring. As far as antibody levels obtained by neutralization and ELISA assays is concerned, a good correlations was noted in 75% of cases. However, in 22 out of 87 sera high levels of neutralizing antibodies were found in association with low ELISA antibody titers or vice versa. These results suggest that screening of adult volunteers should be performed by means of a neutralization assay prior to administration of a candidate vaccine. However, in the absence of such preliminary testing, male volunteers should be chosen since there is a higher probability of low pre-existing antibody levels among such subjects.

Adult↗

Immune response in BALB/c mice following immunization with heat-killed Mycobacterium lepraemurium.

BALB/c mice were immunized with 1 X 10(7) heat-killed Mycobacterium lepraemurium (Mlm) via the hind foot pad. Four weeks later, the animals were infected with 1 X 10(9) Mlm intraperitoneally. Skin test studies, using footpad swelling as a parameter, indicated the development of skin reactivity to Mlm and M. leprae cell extracts. Immunized animals that were infected showed positive reactions to both antigens by the second week. This persisted up to fourteen weeks, at which time, bacillary restriction was also observed in the spleens and livers. Non-immunized infected animals, on the other hand showed a decline in skin reactivity to the two antigens used, and also showed proliferation of Mlm in the two organs examined. Animals receiving heat-killed Mlm or sensitized splenocytes when challenged with 5 X 10(3) M. leprae via hind foot pad, did not show inhibition of the infecting agent, thus indicating a lack of cross-protection.

Animals↗

Direct and indirect actions of 5-hydroxytryptamine on the rat isolated vas deferens.

The contractile effect of 5-hydroxytryptamine on the rat isolated vas deferens was analyzed. In tissues from reserpine-pretreated animals 5-hydroxytryptamine (1 X 10(-6) M-3 X 10(-4) M) induced effects which were much lower than those induced in tissues from normal animals; the effects of low and medium concentrations of 5-hydroxytryptamine were antagonized by methysergide, those of medium and high concentrations were inhibited by phentolamine. In tissues from normal animals 5-hydroxytryptamine-induced contractions were compared with those induced by noradrenaline. 5-Hydroxytryptamine was less potent than noradrenaline and exhibited tachyphylaxis when the time interval between two successive exposures was too short. Phentolamine and dihydroergocristine reduced the effects of 5-hydroxytryptamine at concentrations lower than those necessary to antagonize noradrenaline-induced effects. Methysergide only reduced the effects of lower concentrations of 5-hydroxytryptamine. Cross-protection experiments showed that when noradrenaline was added before dibenamine, responses to both 5-hydroxytryptamine and noradrenaline were maintained to a very similar degree, while when 5-hydroxytryptamine was used as a protecting agent only a small degree of protection was found both towards noradrenaline and 5-hydroxytryptamine-induced effects. Cocaine potentiated the effects of low concentrations of 5-hydroxytryptamine while inhibiting those of high concentrations. The present study provides direct and indirect evidences that the contractile effect of 5-hydroxytryptamine on the rat vas deferens is prevailingly due to the release of noradrenaline; in the lower part of the concentration-response curve also direct effects are involved which are mediated by an interaction with both tryptaminergic "D" receptors and alpha 1-adrenoceptors.

Animals↗

Antigens and toxic components of Legionella in pathogenesis and immunity.

Legionellae are opportunistic facultative intracellular pathogens with several antigens and toxic components which may function synergistically in contribution to pathogenesis and immunity. The serogroup specific antigens are associated with endotoxic activities of the bacteria and are potent adjuvants in inducing hypersensitivity and potentiating antibody responses to various antigens. Two protein toxins interfere with oxidative metabolism of host cells and are potential inhibitors of intracellular bactericidal activities. Tissue damage in the host appears to be caused by lysis of infected cells with release of toxic substances of host and bacterial origins. In host defense, the serogroup antigens provide primarily group-specific immunity, and the acid soluble protein toxin induces cross-protection among different serogroups. The combined effects of antibodies to these antigens in promoting phagocytosis and abrogating toxicity would enhance intracellular killing of the invading bacteria. The serogroup antigen complexes may also function as a potent adjuvant to modulate host responses to the invading bacteria.

Animals↗

Lysates of turkey-grown Pasteurella multocida: effects of solubilizing agents on the immunologic properties of membrane vesicles.

Membrane vesicles from lysed suspensions of turkey-grown Pasteurella multocida were treated with various solubilizing agents to release protein that may contain cross-protection factor. Potassium thiocyanate, NaOH-glycine, lithium diiodosalicylate, guanidine hydrochloride, n-butanol, dimethyl sulfoxide, Triton X-100, and sodium lauryl sarcosinate were each tested as solubilizing agents. Vaccines made from combining solubilized membrane vesicles with complete lysate supernatant fluid produced various degrees of protection against challenge exposure with a heterologous serotype of P multocida in turkeys. Only vaccines prepared from membranes that were solubilized with potassium thiocyanate and sodium lauryl sarcosinate protected as well as complete lysate from turkey-grown P multocida. The amount of protein in each vaccine did not relate to protection. Distinct chemical differences were observed between lysates prepared from turkey-grown P multocida and lysates prepared from 41 C broth-grown P multocida. The external morphology of P multocida, after treatment with lysozyme and EDTA, was similar whether grown in broth or in turkeys.

Animals↗

Attempts to immunise sheep against Ostertagia circumcincta with irradiated larvae.

Mature sheep immunised with two doses of 10,000 irradiated Ostertagia circumcincta larvae were only slightly resistant to challenge with a single dose of 10,000 larvae. This slight resistance was abolished if the 'vaccine' worm population was removed one week before challenge. In contrast, seven of eight sheep immunised with irradiated Haemonchus contortus larvae were highly resistant to homologous challenge. Evidence of some cross protection against challenge with O circumcinta was observed in five of six sheep immunised with irradiated H contortus in that egg counts were lower and more worms were retarded as fourth stage larvae.

Animals↗

[Dengue outbreak by virus type 4 in French Polynesia. II. Preliminary biological observations on epidemiology and physiopathology of the disease (author's transl)].

Authors report some accurate epidemiologic and physiopathologic data about dengue 4. Thanks to virus intrathoracic inoculation in Toxorhynchites amboinensis (Doleshall, 1857), 202 viral strains have been isolated from 633 sera samples. The incidence of the disease has decreased very early after immunization of the whole population and resulted in an eradication of dengue type 1 virus which was endemic in French Polynesia since 1976. Only one type of dengue virus seems to be tolerated in French Polynesian ecosystem in the same time. There is no crossing protection with dengue 1. Clinically, the picture has been the same in both new and previously infected by dengue 1 patients. Duration of viremia during the secondary dengue fever is not shorter than in the primary one. The hemagglutination inhibiting antibodies do not protect patients, but do not result in immune-complexes pathology.

Antibodies, Viral↗

Cytotoxic T cells in HIV2 seropositive Gambians. Identification of a virus-specific MHC-restricted peptide epitope.

A preliminary study of gag-specific, MHC-restricted CD8+ CTL has been performed in nine Gambian patients infected with HIV2. Such CTL were present in at least 55% of patients in fresh peripheral blood mononuclear cells without the requirement for in vitro restimulation. We have identified a nonamer peptide from HIV2 gag that is recognized by CD8+ HLA-B53 CTL using an amino acid sequence motif predicted from analysis of endogenous peptides eluted from HLA-B53 molecules. This peptide, from an HIV2/SIV conserved sequence, has previously been reported to be recognized by CTL from non-human primates vaccinated with recombinant vaccinia virus expressing the gag protein of SIV or infected with SIV virus. HLA-B53-restricted, HIV2 gag-specific CTL did not recognize target cells expressing HIV1 gag proteins, indicating that no cellular cross protection to HIV1 could be expected in this case.

Amino Acid Sequence↗

Isolation and characterization of a Haemophilus paragallinarum mutant that lacks a hemagglutinating antigen.

In an in vivo cross-protection test with Haemophilus paragallinarum strains of serovars B and C, we isolated and characterized a mutant strain, S1M, which lacked a hemagglutinating (HA) antigen when compared biologically and immunologically with isogenic strain S1. Unlike the isogenic strain S1, the mutant strain S1M lacked HA activity against formaldehyde-fixed chicken erythrocytes, even after hyaluronidase treatment, and it did not stimulate hemagglutination-inhibition antibody in chickens immunized with bacterial cells. Dot-blot testing and immunoelectron microscopy with monoclonal antibodies against serovar C-specific HA antigens showed that strain S1M did not react with these monoclonal antibodies. Furthermore, strain S1M was found to be both non-pathogenic and non-immunogenic. In contrast, the isogenic strain S1 reacted with these monoclonal antibodies and was pathogenic and immunogenic. These results suggest that the HA antigen of H. paragallinarum serovar C. strain plays an important role in pathogenicity and immunogenicity.

Animals↗

Integrated management of plant viral diseases.

Viral diseases of plants cause enormous economic losses particularly in the tropics and semitropics which provide ideal conditions for the perpetuation of viruses and their vectors. Intensive agricultural practices necessitated by the ever-increasing demands of the rapidly growing population and the introduction of new genotypes, cropping patterns and crops have further aggravated the problem of viral diseases. Many diverse approaches have been tried to minimize the losses caused by these diseases. The approaches are mainly based on avoidance of sources of infection; avoidance or control of vectors; modification of cultural practices; use of resistant varieties obtained though conventional breeding procedures; cross protection; systemic acquired resistance; and use of transgenic plants containing alien genes that impart resistance to viruses. Although the use of resistant varieties has been found to be the most economical and practical, for effective management of viral diseases an integrated approach is essential in sustainable agriculture. Development of integrated management practices also requires correct identification of the causative viruses, because symptoms can be misleading, and adequate understanding of the ecology of viruses and their vectors.

Animals↗

Pathogenicity and immunity studies of Haemophilus parasuis serotypes.

After intranasal inoculation of SPF pigs with the 7 reference strains of Haemophilus parasuis only the reference strains of serotypes 1 and 5 proved to be pathogenic and were able to produce the lesions characteristic of Glässer's disease. Even though the reference strains of serotypes 2, 3, 4, 6 and 7 proved to be apathogenic, intranasal inoculation resulted in the development of circulating antibodies as demonstrated by the complement fixation test. This serological response suggests an antigenic relationship between serotypes 1 and 3 different from the relationship seen among serotypes 2, 4, 5, 6 and 7. Pigs given an aerosol with the apathogenic serotypes 2, 3, 4 and 7, respectively, resisted challenge with a virulent Danish strain of serotype 5. These results indicate that the 7 serotypes also have antigenic determinants in common and that these determinants elicit cross-protecting immunity on the respiratory mucosa.

Animals↗

[Bacterial endotoxins: relationship between chemical structure and biological effect].

Gram-negative bacteria carry on their surface endotoxins, which are essential for bacterial growth and survival. If released from the bacterial cell, endotoxins induce in higher organisms a great variety of pathophysiological effects. Chemically, endotoxins constitute lipopolysaccharides (LPS), the lipid component (termed lipid A) of which is responsible for the induction of endotoxin effects. The structural and conformational parameters, endowing lipid A with its potent bioactivity, have been well characterized. The toxic effects of endotoxins are initiated by the specific interaction of lipid A with macrophages/monocytes resulting in the production of peptide or lipid mediators. This interaction is governed by a unique (toxic) conformation of lipid A on the one hand, and by specific cellular receptors on the other. The interaction and subsequent mediator production can be specifically and antagonistically inhibited by lipid A partial structures. A recently developed monoclonal anti-LPS-antibody cross-reacts with endotoxins of various bacterial origin, and it cross-protects against harmful endotoxin effects such as pyrogenicity and lethality.

Animals↗

A lipid-conjugated immunostimulating complex subunit vaccine against Salmonella infection in turkeys.

Immunostaining complexes (ISCOMs) are multimeric particles and have been used successfully for presentation of membrane proteins. In this study, outer-membrane proteins (OMPs) from Salmonella heidelberg were incorporated into lipid-conjugated ISCOM particles and evaluated for their use in a vaccine for turkeys against homologous and heterologous Salmonella challenge. Two types of lipid-conjugated ISCOMs were examined: ISCOM-phospholipid and ISCOM-sphingolipid preparations. The turkeys were challenged with one of the three Salmonella serotypes: S. heidelberg, S. reading, or S. enteritidis. The turkeys were monitored for clinical signs, shedding pattern post-challenge, and clearance of the challenge Salmonella from selected internal organs. Vaccines containing OMP with either lipid-conjugated ISCOM preparation produced significantly greater (P < 0.01) immune response than OMP alone. Cloacal swabs from turkeys given OMP along with ISCOM-phospholipid and challenged with a homologous serotype were completely negative for Salmonella. A certain degree of cross-protection against heterologous Salmonella was afforded by both OMP-ISCOM vaccines. The isolation rate of Salmonella from internal organs was significantly lower (P < 0.0001) in vaccinated turkeys than in unvaccinated controls.

Animals↗

Immunogenicity of chemically induced murine colon cancers.

The antigenicity and immunogenicity of three colorectal carcinomas induced in BALB/c mice by 1,2-dimethylhydrazine or N-methyl-N-nitrosourethan were studied. All tumors were readily transplantable. Two of these tumors metastasized when transplants reached sufficient size. All tumors were found to be immunogenic in the strain of origin, and all tumors were shown to contain unique tumor-specific transplantation antigens in cross-protection experiments. The use of these tumors as an animal model for studies of adjuvant immunotherapy and chemoimmunotherapy is suggested.

Animals↗

Pathogen coexistence induced by density-dependent host mortality.

A model of two competing infectious diseases with complete cross-protection sharing one host allows for coexistence, provided that the host population is subject to strong density regulation. The phenomenon is caused by the different ways in which host density affects transmission rate and transmission period. The analysis suggest that disease coexistence is most likely when the two diseases differ significantly in virulence and transmission and that the evolutionary stability of the two-disease association depends critically on details in the functional relationship between virulence and transmission.

Animals↗

Characterization of the alfalfa mosaic virus strain T6.

A strain T6 of alfalfa mosaic virus (AlMV) was characterized. It was isolated from field grown lucerne. Purified virus preparations contained four types of particles, B, M, Tb and Ta, containing separately encapsidated ssRNAs 1 to 4. The strain T6 was able to infect 40 different plant species of 9 families, and to develop a systemic infection in most of them. The symptomatology on bean and the RNA mobility of the AlMV strains T6 and 425 were compared. The classical cross-protection experiments on bean have shown that plants inoculated with strain 425 did not develop symptoms of the challenge strain T6.

Alfalfa mosaic virus↗

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains isolated in southern Taiwan.

The antimicrobial susceptibilities and serotypes of 115 Streptococcus pneumonia strains isolated in southern Taiwan from January 1990 to December 1993 were determined. All isolates were susceptible to cephalothin, cefotaxime, trimethoprim/sulfamethoxazole and vancomycin, and 14 of the isolates were resistant to penicillin G. The oxacillin disk method for presumptive detection of resistance to penicillin had a sensitivity of 85.7% and specificity of 97.0%. Resistance rates were as follows: erythromycin 62.2%, tetracycline 71.3%, clindamycin 46.1% and chloramphenicol 19.1%. Eighty-four percent of the isolates were resistant to one or more of the antibiotic tested. Multiple resistance (to three or more classes of antibiotics) was identified in 40.9% of all the isolates and 100% of penicillin-resistant isolates. The predominant serotypes were: 14 (19.1%), 3 (17.4%), 23 (15.7%), 6 (10.4%), and 15 (6.1%). Serotypes 14 and 63 most commonly caused childhood infections, while serotypes 3 and 23 were frequently encountered in adults. The proportion of coverage in 23-valent pneumococcal polysaccharide vaccine was 92.2%, if vaccine-related serotypes were considered to be cross-protecting. Seven (58%) of 12 typable penicillin-resistant isolates belonged to serotype 23 and two (16.7%) to serotype 6. All isolates of serotype 14, 23, 15 and 19 were resistant to one or more antibiotics. Multiple drug resistance was frequently associated with serotype 23 (31.9%), 14 (23.4%) and 6 (17.0%). Sixty-five percent of isolates of serotype 3 were susceptible to all antibiotics tested. The high level of antimicrobial resistance in S. pneumoniae mandates the continuous surveillance of resistance and the strict control of antibiotic use in Taiwan.

Adult↗

Antigenic characterization of an Arkansas isolate of infectious bursal disease virus.

The s977 strain of infectious bursal disease virus (IBDV) was isolated in northwest Arkansas in 1977 from the bursae of young broilers with high maternal antibody titers to the Moulthrop strain of IBDV (BursaVac). The comparison of a plaque-purified isolate of s977 with other IBDV serotype 1 and serotype 2 strains using virus neutralization indicates that s977 is a subtype of serotype 1 vaccine viruses and the MD variant strain of IBDV and has no relatedness to the Delaware Variant A (VarA) virus. In vivo cross-protection studies in specific-pathogen-free white leghorn chickens showed that an inactivated vaccine using s977 antigen was 2.5 times more protective against challenge with s977 than was an inactivated IBDV Variant E (VarE) vaccine. The vaccination of maternally immune broiler chicks with live s977 did not provide protection against subsequent challenge, indicating that s977 does not have enough antigenic difference to break through maternal immunity. Analysis of denatured viral polypeptides using polyacrylamide gel electrophoresis showed that s977 and two reported variant strains, 51 and VarE, share three protein bands, 90 kD (VP1), 40 kD (VP2), and 31 kD (VP3), that were not observed in BursaVac. BursaVac and s977 shared a 74 kD precursor band that was absent or very faint in the VarE and 51 strains. The most unique characteristic of s977 was the relative abundance of a wide, 56-63 kD band that contained two distinct immunoreactive bands when blotted with antiserum to s977. BursaVac contained a 56 kD band that failed to react with s977 antiserum. Analysis of polypeptide bands using laser densitometry indicated the presence of a number of bands between 20 kD and 25 kD in the s977, 51, and VarE preparations but only a 25 kD band in BursaVac. The number of bands decreased with the degree of relatedness to standard vaccine strains. It appears that, antigenically, S977 may hold an intermediate position between the classic virus strains and the more recently reported serotype 1 variants.

Animals↗