Parasite features impeding malaria immunity: antigenic diversity, antigenic variation and poor immunogenicity.
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Bacteroides forsythus is one of the etiologic agents of destructive periodontal diseases. Determining which antigenic components of the bacterium are recognized in the immune response of periodontitis patients is an important step in assessing strategies for vaccine development. The aim of this study was to identify the major strain-variable and cross-reactive antigens of B. forsythus clinical isolates recognized by serum IgG from patients with early-onset rapidly progressive periodontitis. Ten patient sera with measurable IgG against antigenic components of the species were identified by Western blot. Positive sera were tested by checkerboard ELISA to identify those most responsive to strain-variable antigens in nine clinical isolates and ATCC strain 43037. Correlation analysis of the ELISA data suggested that different subsets of isolates were preferentially recognized by different sera. Western blots revealed that certain sera also recognized major shared components across all the isolates, but preferential recognition of different isolate subsets by different patients was clearly confirmed. To determine if the variable antigens recognized were nonprotein, proteinase K-digested isolates were compared to undigested controls by Western blot. The main strain-variable antigens were proteinase resistant, while proteins at 200 and 210 kDa were identified as the major shared components. Two-dimensional SDS-PAGE revealed that these proteins are the quantitatively dominant heat-modifiable components of the cell envelope. Even though variable antigens are prominent in the immune response of patients, a cross-protective vaccine based on the shared envelope proteins of B. forsythus seems feasible in light of these observations.
A total of 16 strains of influenza A virus isolated in 1965-66 from quail, ducks, turkeys, pheasants and chickens bred in poultry farms situated in Pavia and surrounding districts in northern Italy were investigated from the point of view of antigenic grouping by the complement-fixation test.All strains were antigenically related but not identical to each other. Most but not all strains were antigenically related to virus N and some to Duck/England/62, Turkey/Canada/63 and Turkey/Massachussets/65. There was a suggestion of an antigenic shift away from virus N but replacement of given strains by subsequent variants was not constant.The findings do not support the view that animal influenza viruses do not show antigenic variation comparable to that seen among human strains. There was no correlation between antigenic structure and host range and thus no indication that different hosts are infected preferentially by viruses of a particular antigenic character.
Nineteen strains of Newcastle disease virus (NDV) isolated from wild ducks in Japan were placed into 4 distinct antigenic groups on the basis of their reactivities to 8 monoclonal antibodies against the HN molecule of NDV in hemagglutination inhibition tests. The NDV strains of duck origin were antigenically distinct from NDV-B1 and NDV-Miyadera originated from chickens, and varied in their virulence to chicken embryos. No apparent correlation was found between the antigenicity of the HN molecule and virulence.
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125I-labelled haemagglutinin (HA) micropeptide mapping and haemagglutinin inhibition (HAI) tests with monoclonal antibodies were used in analysing antigenic variation of six strains of influenza A virus isolated from 1972 to 1983 in China. The results from micropeptide mapping generally coincided with those of sequence analysis. 125I-labelled HA micropeptide mapping is a simple, reproducible and practical method for surveillance of influenza, especially in combination with HAI test using monoclonal antibodies.
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Consideration of information published on the immunology of malarial parasites has highlighted an unusual problem associated with the penetration of erythrocytes by merozoites, namely, how to reconcile strain and intrastrain antigenic variation in the parasite surface with recognition of specific receptors on red cells. This problem should now be susceptible to experimental investigation.
Erythrocytes infected with mature asexual stages of Plasmodium knowlesi express a new surface antigen such that rhesus monkey antisera specifically agglutinate these cells. Cloned parasites can express different antigenic variants of this antigen. The variant antigen has been identified by comparison of the surface membrane antigens of a clone and of an antigenic variant of that clone of different agglutination phenotype. After lactoperoxidase labeling, 125I-labeled proteins of Mrs 210,000 and 190,000 with one clone and of Mrs 205,000 with the antigenic variant were only immunoprecipitated by antisera containing homologous anti-variant antibody. Antigens of the same Mr from each clone were labeled by [35S]methionine incorporation during parasite growth and also specifically immunoprecipitated only by agglutinating antisera. Therefore, the variant antigens are malarial proteins rather than modified host proteins.
Neonatal mice (CR:NIH:S) were infected with a cloned human isolate of Giardia lamblia (GS/M-83-H7) and the surface antigens of the intestinal trophozoites, as well as the cellular and humoral immune responses, were analysed during the course of infection. Infections in mice peaked 2-3 weeks after inoculation and were self-cured by day 42 post-infection (p.i.). The proportion of trophozoites expressing the Mr 72,000 surface antigen of the initial inoculum had decreased by day 12 and approached zero by day 22 p.i., similar to infections in humans. The predominant parasite-specific humoral response was an IgM- and IgG-isotype directed to the original Mr 72,000 surface antigen as well as other antigens. T-lymphocytes (predominantly LY4(CD4)+) isolated from Peyer's patches 12 days p.i. and later showed a significant proliferative response to Giardia lamblia antigens. Spleen and lymph node cells showed no lymphoproliferative response. T-cell blot analysis revealed the presence of dominant T-cell epitopes in the areas of Mr 200,000-75,000 and less than 50,000 polypeptides. No response was demonstrated in the Mr 72,000 region (migration site of the major surface antigen), suggesting T-cell dependent mechanisms are most likely not responsible for the surface antigen switch which occurred during the course of infection. This model infection can be used to study the role of immunological mechanisms in Giardia lamblia variant antigen switching and in the control of infections.
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The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant outer membrane protein, major surface protein 2 (MSP2), involved in antigenic variation and long-term persistence of the organism in carrier animals. MSP2 contains a central hypervariable region of about 100 amino acids that encodes immunogenic B-cell epitopes that induce variant-specific antibodies during infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA transcript in erythrocyte stages of A. marginale and defined the structure of the genomic expression site for this transcript. In this study, we show that the same expression site is utilized in stages of A. marginale infecting tick salivary glands. We also analyzed the variability of this genomic expression site in Oklahoma strain A. marginale transmitted from in vitro cultures to cattle and between cattle and ticks. The structure of the expression site and flanking regions was conserved except for sequence that encoded the MSP2 hypervariable region. At least three different MSP2 variants were encoded in each A. marginale population. The major sequence variants did not change on passage of A. marginale between culture, acute erythrocyte stage infections, and tick salivary glands but did change during persistent infections of cattle. The variant types found in tick salivary glands most closely resembled those present in bovine blood at the time of acquisition of infection, whether infection was acquired from an acute or from a persistent rickettsemia. These variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.
N1 influenza virus neuraminidases (NA) derived from avian, swine and human virus isolates, including the genetically related classic strains A/FPV/Rostock/34, A/Swine/1976/31, A/PR8/34 and A/FM1/47, were analysed serologically by neuraminidase inhibition (NI), inhibition of virus release (IVR) and competitive radio-immunoassays (competitive RIA). Comparing the three tests, competitive RIA appeared to be more reliable than NI and IVR for a quantitative assessment of antigenic relatedness. Together with evidence presented by others, these studies indicate that the host species contributes to the extent of antigenic variation of NAses. In contrast to NAses of human viruses where antigenic drift occurs readily, NAses of animal influenza viruses, from birds or mammalians, undergo far fewer antigen changes.
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