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Results for “Cross Protection”

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PubMed1998

Molecular inhibition of HIV type 1 by HIV type 2: effectiveness in peripheral blood mononuclear cells.

HIV-2 downregulates HIV-1 in human primary peripheral blood mononuclear cells (PBMCs). Although the effect of HIV-2 on HIV-1 in human CD4+ T cell lines was previously reported, the present observations with PBMCs are a necessary demonstration before considering animal model and clinical studies. Notably, the downregulation was observed with at least three phenotypically different HIV-1 proviruses and three different HIV-2 proviruses and was independent of the mode of introduction of the proviruses. HIV-2 inhibited both the production of extracellular HIV-1 p24 antigen and intracellular viral RNA, suggesting the involvement of transcriptional downmodulation. Some of the defective HIV-2 proviruses also inhibited HIV-1. In some cases, these defects were transcomplemented by the corresponding HIV-1 gene products, emphasizing cross-regulation between the two viruses. The phenotype of one of the mutant HIV-2 proviruses suggested that the posttranscriptional effects may also occur. In addition to the possible HIV-2 suppression of HIV-1 in vivo by cross-protective immune mechanisms, intracellular inhibition, noted here, may be another line of defense. We have proposed that the inhibition may be the result of competition between HIV-1 and HIV-2 for cellular factors, possibly involving the long terminal repeats (LTRs). For safety reasons, it may be advantageous to use subunits of HIV-2 for vaccines and gene therapy. HIV-2, specifically noncytopathic HIV-2, could be viewed as an attenuated HIV-1 vaccination model. HIV-2-derived gene transfer vectors may not only be inhibitory themselves but also allow for the insertion of additional protective genes to aim at multiple targets in the HIV-1 life cycle, thus curtailing the evolution of escape mutants.

Antibiosis↗

PubMed2000

European experience with the West Nile virus ecology and epidemiology: could it be relevant for the New World?

A review of West Nile virus (WNV) and the epidemiology of West Nile fever (WNF) in Europe is presented. European epidemics of WNF reveal some general features. They usually burst out with full strength in the first year, but few cases are observed in the consecutive 1 to 2 (exceptionally 3) years, whereas smaller epidemics or clusters of cases only last for one season. The outbreaks are associated with high populations of mosquitoes (especially Culex spp.) caused by flooding and subsequent dry and warm weather, or formation of suitable larval breeding habitats. Urban WNF outbreaks associated with Culex pipiens biotype molestus are dangerous. Natural (exoanthropic, sylvatic) foci of WNV characterized by the wild bird-ornithophilic mosquito cycle probably occur in many wetlands of climatically warm and some temperate parts of Europe; these foci remain silent but could activate under circumstances supporting an enhanced virus circulation due to appropriate abiotic (weather) and biotic (increased populations of vector mosquitoes and susceptible avian hosts) factors. It is very probable that WNV strains are transported between sub-Saharan Africa and Europe by migratory birds. The surveillance system for WNF should consist of four main components: (1) monitoring of mosquito populations and their infection rate; (2) wild vertebrate surveys; (3) sentinel birds (domestic ducks rather than chickens); and (4) monitoring of human disease. In the case of persisting high risk of WNF for humans and equids in certain enzootic areas, immunization against WNF should be considered. For that purpose a commercially available, cross-protective vaccine against Japanese encephalitis could be used.

Animals↗

PubMed2003

Stress-induced gene expression in Candida albicans: absence of a general stress response.

We used transcriptional profiling to investigate the response of the fungal pathogen Candida albicans to temperature and osmotic and oxidative stresses under conditions that permitted >60% survival of the challenged cells. Each stress generated the transient induction of a specific set of genes including classic markers observed in the stress responses of other organisms. We noted that the classical hallmarks of the general stress response observed in Saccharomyces cerevisiae are absent from C. albicans; no C. albicans genes were significantly induced in a common response to the three stresses. This observation is supported by our inability to detect stress cross-protection in C. albicans. Similarly, in C. albicans there is essentially no induction of carbohydrate reserves like glycogen and trehalose in response to a mild stress, unlike the situation in S. cerevisiae. Thus C. albicans lacks the strong general stress response exhibited by S. cerevisiae.

Candida albicans↗

PubMed2004

A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans.

Previous work has implicated the Hog1 stress-activated protein kinase (SAPK) in osmotic and oxidative stress responses in the human pathogen Candida albicans. In this study, we have characterized the role of Hog1 in mediating these and other stress responses in C. albicans. We provide evidence that a SAPK-dependent core stress response exists in this pathogen. The Hog1 SAPK is phosphorylated and it accumulates in the nucleus in response to diverse stress conditions. In addition, we have identified Hog1-regulated genes that are induced in response to stress conditions that activate Hog1. These analyses reveal both activator and repressor functions for the Hog1 SAPK. Our results also demonstrate that stress cross-protection, a classical hallmark of the core stress response, occurs in C. albicans between stresses that activate the Hog1 SAPK. Importantly, we find that the core stress response in C. albicans has adapted to the environmental niche of this human pathogen. This niche specificity is reflected by the specific environmental conditions that drive the Hog1-regulated core stress response in C. albicans and by differences in the molecular circuitry that control this response.

Base Sequence↗

PubMedDate not supplied

Disease exacerbation caused by sequential dengue infections: myth or reality?

Dengue can be caused by any one of four viruses that are antigenically related but not cross-protective. It has been proposed that the disease may be more severe if an infection with one dengue serotype follows infection with another serotype. Both experimental and epidemiologic data have been cited to substantiate this concept, but the present reviewer does not find the data convincing. The issue is of practical importance because of its relevance to the use of dengue vaccines now under development. It is impossible to prove that clinical manifestations of dengue are not exacerbated by sequential infections. Negative findings can always be countered by arguments that exacerbation occurs only with certain serotypes, only with certain strains of those serotypes, or only when infections occur at critical intervals. Interested persons can examine the relevant data and decide whether the concept of disease exacerbation following sequential dengue infections is myth or reality.

Dengue↗

PubMedDate not supplied

Experimental leishmaniasis in humans: review.

Experimental infection of humans with Leishmania parasites has contributed significantly to the understanding of the etiology, transmission, and pathogenesis of leishmaniasis and the immunity associated with it. Leishmania organisms recovered from human and animal tissue, insect vectors, and in vitro cultures have all produced cutaneous or visceral leishmaniasis in human subjects who were voluntarily inoculated with them. Volunteers bitten by infected Phlebotomine sandflies also developed cutaneous or visceral disease. In these experiments, it appeared that the parasite must undergo certain developmental changes within the sandfly for it to become infective and that the parasites in sandflies were far more efficient in causing full-blown infection than were cultured Leishmania organisms. The clinical manifestations of these experimental infections did not differ from infections that were acquired naturally. Natural or experimental infections appeared to confer resistance to subsequent leishmanial infection. This immunity was best documented to be a species-specific phenomenon; however, a small number of studies have demonstrated cross protection between some Leishmania species. In this review article, data from human experimental infections are summarized and discussed in light of recent advances in the field.

Animals↗

PubMed1996

Immunogenicity and efficacy of Streptococcus pneumoniae polysaccharide-protein conjugate vaccines against homologous and heterologous serotypes in the chinchilla otitis media model.

Cross-protection among pneumococcal serotypes within serogroups was measured in the chinchilla otitis media (OM) model because several serotypes that cause OM in children are closely related biochemically. Chinchillas were given tetravalent vaccine composed of pneumococcal capsular polysaccharides (PS; types 6B, 14, 19F, 23F) conjugated to an outer membrane protein complex, and 89% to 96% developed a > or = 2-fold serum IgG rise against vaccine PS. Vaccine efficacy was tested by inoculating middle ear hypotympanic bullae with Streptococcus pneumoniae types 6B, 6A, 19F, or 19A. OM severity in the vaccinated groups challenged with types 6B, 6A, and 19F but not 19A was significantly better than in the respective placebo groups. Culture-positive pneumococcal OM occurred in 38%, 62%, 0, and 78% of vaccinated chinchillas challenged with types 6B, 6A, 19F, and 19A, respectively, but in 88% of type 6B- and 100% of type 6A-, 19A-, and 19F-challenged placebo chinchillas.

Analysis of Variance↗

PubMed1999

Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities.

The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of sIgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Peptide 145-specific sIgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific sIgA increases with age, consistent with a role for such antibodies in immunity to GAS. Human sIgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization of GAS was totally dependent on the presence of both complement and polymorphonuclear leukocytes, and, moreover, affinity-purified p145-specific sIgA was shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an important role in human immunity against GAS and may be useful in a broad-based cross-protective anti-streptococcal vaccine.

Adolescent↗

PubMed2004

Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria.

OBJECTIVES: This study was undertaken to analyse incidence rates, serotype distribution and antimicrobial resistance patterns of invasive Streptococcus pneumoniae isolates from hospitalized children up to 5 years of age with invasive pneumococcal disease (IPD), including meningitis, in Austria. METHODS: From February 2001-January 2003, nationwide prospective surveillance was conducted that included all paediatric hospitals and clinical microbiological laboratories. All invasive pneumococci isolated were serotyped and tested for antimicrobial susceptibility. RESULTS: The mean annual incidence rates of IPD per 10 000 population for the age groups <24 months and <60 months were 14.5 (7.7 for meningitis) and 13.7 (6.0 for meningitis), respectively. The case fatality rate was 6% for IPD and 12% for meningitis. Of all IPD cases, 69.6% (73.1% for meningitis) were covered by serotypes and 83.9% (88.5% for meningitis) by cross-protection of vaccine-related serotypes. Intermediate penicillin G susceptibility (MIC 0.12-1 mg/L) was found in 12/56 strains. No penicillin G-resistant strains were found. A total of 19/56 isolates showed decreased susceptibility to macrolide agents (MIC >/= 1 mg/L). CONCLUSIONS: The IPD incidence rate was similar, and serotype coverage of the 7-valent conjugated vaccine marginally superior, to Germany. The surprisingly high level of antimicrobial resistance among invasive isolates considerably amplifies the potential impact of a childhood pneumococcal vaccination programme in Austria.

Anti-Infective Agents↗

PubMed2002

Tetravalent rhesus-human rotavirus vaccine (RRV-TV) in Belém, Brazil: efficacy against prevailing P and G genotypes.

To determine the efficacy of a reassortant rhesus-human tetravalent rotavirus vaccine (RRV-TV) (4 x 10(4) pfu/dose) against P and G rotavirus genotypes, 90 positive samples were tested using reverse transcription-polymerase chain reaction. The efficacy of the RRV-TV vaccine against P[8] and G1 individually or in binary combination P[8], G1 was 72 per cent (p < 0.005) 61 per cent (p < 0.013), and 70 per cent (p < 0.009), respectively, only for the first year of follow-up. In the second year, as well as after 2 years of follow-up, no efficacy was observed to these genotypes. These data indicate that further studies with rotavirus vaccines should focus on the molecular characterization of rotaviruses genotypes, in order to see whether or not cross-protection among different G and P genotypes may occur as a result of common bearing of VP4 specificities.

Brazil↗

PubMed1990

Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality. Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible. The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established. This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis.

Animals↗

PubMed2002

Pneumococcal serotypes from acute otitis media in rural Kentucky.

OBJECTIVE: Acute otitis media (AOM) accounts for most infections caused by, but few data are available regarding the incidence of pneumococcal serotypes recovered from children with AOM in the United States. METHODS: Between January 1992 and March 1998, 777 middle ear pathogens from AOM were obtained from 701 patients by tympanocentesis (84.6%) or by culture of otorrhea (15.4%) from spontaneous perforation or draining tubes. The ambulatory patient population was mostly white and cared for by a sole private pediatric practice in rural Kentucky. RESULTS: Penicillin-nonsusceptible (penicillin MIC > or = 0.1 microg/ml) (PNSP) isolates accounted for 18% [6% resistant PNSP (rPNSP) and 12% intermediate resistant PNSP], and penicillin-susceptible strains accounted for 35% of the pathogens recovered from children with culture-proved AOM. Comparing the frequency of isolates between 1992 and 1993 with those between 1994 and 1998, overall rates of PNSP strains remained remarkably stable (32.2% 37.3%), but intermediate resistant PNSP strains doubled from 14% to 27% ( < 0.01), whereas rPNSP strains fell by one-third. Serotypes 19F (34%), 23F (30%), 6B (26%) and 14 (8%) accounted for nearly all rPNSP isolates. Two cross-reactive serotypes (6A and 19A) not included in the available pneumococcal conjugate vaccine comprised 8.4 and 15% of all serotypes and PNSP serotypes, respectively. Nearly all PNSP strains recovered in children < or =24 months are included in the vaccine serogroups. CONCLUSION: Depending on rates of efficacy and serotype cross-protection, the current pneumococcal conjugate vaccine could potentially protect against most PNSP strains in all ages, particularly in those < or =24 months.

Age Factors↗

PubMed1982

Heterogeneity of tumorigenicity phenotype in murine tumors. Characterization of tumor clones isolated from primary 3-methylcholanthrene-induced fibrosarcomas.

In this study we have characterized three series of clonal populations isolated from primary murine fibrosarcomas induced with three different doses of the chemical carcinogen, 3-methylcholanthrene (3-MCA). Clones were evaluated fro their in vivo growth rates after transplantation into normal syngeneic animals, and for immunological cross-protection toward clones derived from the same tumor. A pattern of reactivity emerged from these studies which supports, at the single-cell level, existing theories regarding the correlation between the inducing dose of chemical carcinogen and the antigenicity of the resulting tumors. Clones from tumors induced with 10 mg of 3-MCA were found to be less tumorigenic than clones from tumors induced with 5 mg of 3-MCA. The 5-mg clones were in turn less tumorigenic than the 1-mg clones, all of which grew rapidly in normal animals. Related clones from each tumor were found for the most part to be immunologically noncross-reactive with other clones from the same tumor, suggesting that subpopulations of tumor cells expressing different tumor-specific transplantation antigens (TSTAs) may reside within single primary tumors. We have used these observations to formulate an hypothesis for the origin of antigenic heterogeneity in 3-MCA-induced tumors and as the basis for a discussion of the relationship between cell transformation and the appearance at the cell surface of tumor-specific transplantation antigens.

Animals↗

PubMed2002

Hepatitis C flare due to superinfection by genotype 4 in an HCV genotype 1b chronic carrier.

We report here on a patient affected by chronic hepatitis C who developed acute hepatitis C virus (HCV) superinfection with replacement of genotype 1b by genotype 4. The history revealed no risk factors for a new exposure to HCV, with the exception of colonoscopy with mucosal biopsy performed about 3 months before. This report underlines the absence of an effective immune-mediated cross-protection against different HCV genotypes. Moreover, the possible relationship between HCV infection and colonoscopy points out the importance of strict adherence to international guidelines for disinfection and cleaning of invasive diagnostic tools for all subjects examined, including HCV chronic carriers.

Adult↗

PubMed1994

Theoretical studies of the effects of heterogeneity in the parasite population on the transmission dynamics of malaria.

Periodicity in malaria transmission has generally been ascribed to seasonal fluctuations in mosquito population density or spatial heterogeneity with periodic migration. In this paper we demonstrate that simple models of strain heterogeneity can generate periodic behaviour as a consequence of the interaction between parasite strains and host immunological defences. As the degree of cross-immunity between strains increases, the system moves from a régime of independent strain transmission and coexistence, through increasingly coupled behaviour, to the displacement of the strain of lower transmissibility by the strain with a higher basic reproductive rate (R0). Cross-immunity thus serves both to bring the strains into competition, and also to couple the dynamics. We find analytical and numerical results on strain coexistence to show how the range of possible outcomes may be read as an effect of the tension between these two effects of cross-protection.

Animals↗

PubMed1992

A viroid from Nematanthus wettsteinii plants closely related to the Columnea latent viroid.

A viroid was isolated from symptomless Nematanthus wettsteinii plants using the return-PAGE method for analysis of low M(r) nucleic acids. The RNA was transmitted to tomato, three cultivars of potato, and Scopolia sinensis plants by mechanical inoculation or by grafting. Infected solanaceous plants developed symptoms similar to those caused by potato spindle tuber viroid (PSTVd). The Nematanthus viroid consists of 372 nucleotides, 214 G+C, 158 A+U, with a G+C/A+U ratio of 1.35. One of seven cDNA clones showed a sequence heterogeneity (G to A) at position 73. The most stable secondary structure of this viroid has 78 G:C, 37 A:U and 11 G:U base pairs with a minimum free energy of -456.9 kJ. The viroid is closely related to the 370 nucleotide Columnea latent viroid. The Nematanthus viroid possesses regions of 100% sequence identity with six viroids belonging to the PSTVd and apple scar skin viroid groups. The viroid also replicated in tomato plants when mixed with PSTVd. Tomato plants were cross-protected against PSTVd when preinfected with the viroid from N. wettsteinii.

Base Sequence↗

PubMed1995

Seroepidemiological and molecular evidence for the presence of two H3N8 equine influenza viruses in China in 1993-94.

In May 1993, a severe epidemic of respiratory disease began in horses in Inner Mongolia and spread throughout horses in China. The disease affected mules and donkeys as well as horses but did not spread to other species, including humans. The severity of the disease raised the question of whether the outbreak might have been caused by the new avian-like influenza viruses detected in horses in China in 1989 or by current variants ofA/equine/Miami/1/63 (H3N8) (equine-2) or by a reassortant between these viruses. Antigenic and sequence analysis established that all gene segments of the influenza virus causing the epidemic were of recent equine-2 origin and that the virus was not a reassortant. Serological analysis of post-infection horse sera provided evidence for the continued circulation of the A/Equine/Jilin/1/89 (Eq/Jilin) (H3N8) avian-like viruses in horses in Heilongjiang province with original antigenic sin-like responses. It is noteworthy that prior infection with the avian-like Eq/Jilin strain did not afford cross-protection against a current equine-2 strain. Serological evidence for the continued circulation of the avian-like H3N8 influenza virus in horses indicates that this virus has probably established itself in horses in Asia.

Animals↗

PubMed1996

The immunological activity of a deletion mutant of influenza virus haemagglutinin lacking the globular region.

A deletion mutant of influenza virus haemagglutinin (HA; headless HA) lacking the globular region was expressed in CV-1 cells and detected with a monoclonal antibody, C179, which recognizes a conformational epitope in the middle of the stem region of HA and neutralizes all H1 and H2 subtypes. The cDNA coding for the headless HA was constructed from influenza virus A/Okuda/57 (H2N2), which was also used to select C179. The conformational epitope recognized by C179 was highly stable even after removal of the globular region. The survival rate of mice immunized with the headless HA and challenged with lethal influenza virus A/FM/l/47 (H1N1) was significantly higher than that of the control mice. The headless HA has the potential to induce cross-protection against influenza virus infection.

Animals↗