Surface antigens on haemoparasites and their relevance to protective immunity

Bovine tuberculosis (bTB) is a highly transmissible infection and remains of great concern as a zoonosis. The worldwide incidence of bTB is in rise, creating potential reservoir and increased infection risk for humans and animals. In attempts to identify novel surface antigens of Mycobacterium bovis as a proof-of-concept for potential inducers of protective immunity, we investigated surface proteome of M. bovis BCG strain that was cultured under the granuloma-like condition. We also demonstrated that the pathogen exposed to the biologically relevant environment has greater binding and invasion abilities to host cells than those of bacteria incubated under regular laboratory conditions. A total of 957 surface-exposed proteins were identified for BCG cultured under laboratory condition, whereas 1,097 proteins were expressed under the granuloma-like condition. The overexpression of Mb1524, Mb01_03198, Mb1595_p3681 (PhoU1 same as phoY1_1), and Mb1595_p0530 (HbhA) surface proteins in Mycobacterium smegmatis leads to increased binding and invasion to mucosal cells. We also examined the immunogenicity of purified recombinant proteins and tested M. smegmatis overexpressing these surface antigens for the induction of protective immunity in mice. Significantly high levels of specific IgA and IgG antibodies were observed in recombinant protein immunized groups by both inhalation and intraperitoneal (IP) routes, but only IP delivery induced high total IgA and IgG levels. We did not detect major differences in antibody levels in the M. smegmatis group that overexpressed surface antigens. In addition, the bacterial load was significantly reduced in the lungs of mice immunized with the combination of inhaled recombinant proteins. Our findings suggest that the activation of the mucosal immunity can lead to increased ability to confer protection upon M. bovis BCG infection.

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Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens

Infection and Immunity ◽

10.1128/iai.72.6.3531-3535.2004 ◽

2004 ◽

Vol 72 (6) ◽

pp. 3531-3535 ◽

Cited By ~ 33

Author(s):

Morten A. Nielsen ◽

Lasse S. Vestergaard ◽

John Lusingu ◽

Jørgen A. L. Kurtzhals ◽

Haider A. Giha ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Protective Immunity ◽

Surface Antigens ◽

African Countries ◽

Variant Surface Antigens ◽

Antibody Recognition ◽

Specific Immunoglobulin ◽

Life Threatening ◽

Specific Igg ◽

Plasma Collection

ABSTRACT The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

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Molecular Aspects ofPlasmodium falciparumInfection during Pregnancy

Journal of Biomedicine and Biotechnology ◽

10.1155/2007/43785 ◽

2007 ◽

Vol 2007 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Nicaise Tuikue Ndam ◽

Philippe Deloron

Keyword(s):

Molecular Basis ◽

Protective Immunity ◽

Surface Antigens ◽

Pathological Process ◽

Sub Saharan Africa ◽

Variant Surface Antigens ◽

Important Exception ◽

Sub Saharan ◽

Molecular Aspects ◽

Poor Outcomes

Cytoadherence ofPlasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSAPAM), including theP. falciparumerythrocyte membrane protein 1 (PfEMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM.

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Genetic Diversity and Antigenic Polymorphism in Plasmodium falciparum: Extensive Serological Cross-Reactivity between Allelic Variants of Merozoite Surface Protein 2

Infection and Immunity ◽

10.1128/iai.71.6.3485-3495.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3485-3495 ◽

Cited By ~ 36

Author(s):

Simon Franks ◽

Luke Baton ◽

Kevin Tetteh ◽

Eric Tongren ◽

David Dewin ◽

...

Keyword(s):

Immune Evasion ◽

Protective Immunity ◽

Direct Evidence ◽

Surface Protein ◽

Surface Antigens ◽

Merozoite Surface Protein ◽

Cross Reactivity ◽

Immune Selection ◽

Allelic Variants ◽

Original Antigenic Sin

ABSTRACT Diversity in the surface antigens of malaria parasites is generally assumed to be a mechanism for immune evasion, but there is little direct evidence that this leads to evasion of protective immunity. Here we show that alleles of the highly polymorphic merozoite surface protein 2 (MSP-2) can be grouped (within the known dimorphic families) into distinct serogroups; variants within a serogroup show extensive serological cross-reactivity. Cross-reactive epitopes are immunodominant, and responses to them may be boosted at the expense of responses to novel epitopes (original antigenic sin). The data imply that immune selection explains only some of the diversity in the msp-2 gene and that MSP-2 vaccines may need to include only a subset of the known variants in order to induce pan-reactive antibodies.

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Genotypic characterization of Egypt enterotoxigenic Escherichia coli isolates expressing coli surface antigen 6

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2454 ◽

2013 ◽

Vol 7 (02) ◽

pp. 090-100 ◽

Cited By ~ 2

Author(s):

Atef M El-Gendy ◽

Adel Mansour ◽

Hind I Shaheen ◽

Marshall R Monteville ◽

Adam W Armstrong ◽

...

Keyword(s):

Escherichia Coli ◽

Surface Antigen ◽

Protective Immunity ◽

Surface Antigens ◽

Enterotoxigenic Escherichia Coli ◽

Mechanisms Of Resistance ◽

E Coli ◽

Colonization Factor ◽

Factor Expression

Introduction: One approach to control enterotoxigenic Escherichia coli (ETEC) infections has been to develop vaccines focused on inducing protective immunity against surface expressed antigenic factors. One such factor is coli surface antigen 6 (CS6); ETEC isolates expressing CS6 may also simultaneously co-express surface antigens CS4 or CS5. However, there is little information regarding the inter-relationships of isolates expressing the CS6 antigen alone or in combination with CS4 or CS5. Methodology: A total of 62 CS6-associated ETEC isolates were evaluated for their antimicrobial susceptibility, mechanisms of resistance, toxin genes, colonization factor expression, and XbaI-pulsed-field gel electrophoretic profiles. Results: We observed 46 XbaI profiles; 31 were exclusive to ETEC expressing CS6 alone and 15 among the ETEC co-expressing CS4 or CS5. Nearly half (47%) of these isolates were resistant to ampicillin, a third (37%) of the isolates were resistant to trimethoprim-sulfamethoxazole, and 24% of the isolates were tetracycline-resistant. A blaTEM gene was detected in 24 (83%) ampicillin-resistant isolates. Trimethoprim-sulfamethoxazole-resistant isolates (n = 23) carried either sulI (n = 1, 4%), sulII (n = 8, 35%) or both genes (n = 10, 43%); 4 had no detectable sul gene. Conclusions: Our results show a lack of clonality among Egypt CS6 E. coli isolates and supports the use and the further research on vaccines targeting this cell surface antigen.

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Cross-protective immunity induced by Babesia bovis clones with antigenically unrelated variable merozoite surface antigens

Veterinary Immunology and Immunopathology ◽

10.1016/0165-2427(94)90108-2 ◽

1994 ◽

Vol 41 (3-4) ◽

pp. 367-374 ◽

Cited By ~ 17

Author(s):

Varda Shkap ◽

Eugene Pipano ◽

Terry F. McElwain ◽

Uri Herzberg ◽

Y. Krigel ◽

...

Keyword(s):

Protective Immunity ◽

Surface Antigens ◽

Babesia Bovis

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Antibody response against schistosomulum surface antigens and protective immunity following immunization with highly irradiated cercariae of Schistosoma mansoni

Parasite Immunology ◽

10.1111/j.1365-3024.1985.tb00065.x ◽

1985 ◽

Vol 7 (2) ◽

pp. 133-152 ◽

Cited By ~ 30

Author(s):

A. J. G. SIMPSON ◽

F. HACKETT ◽

T. WALKER ◽

R. ROSSI ◽

S. R. SMITHERS

Keyword(s):

Antibody Response ◽

Schistosoma Mansoni ◽

Protective Immunity ◽

Surface Antigens

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VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria

Parasitology ◽

10.1017/s0031182007000121 ◽

2007 ◽

Vol 134 (13) ◽

pp. 1871-1876 ◽

Cited By ~ 41

Author(s):

L. HVIID ◽

A. SALANTI

Keyword(s):

Immune Response ◽

Plasmodium Falciparum ◽

Pregnant Women ◽

Protective Immunity ◽

Plasmodium Falciparum Malaria ◽

Surface Antigens ◽

Variant Surface Antigens ◽

Important Target ◽

First Time ◽

Stable Transmission

SUMMARYPeople living in areas with stable transmission of P. falciparum parasites acquire protective immunity to malaria over a number of years and following multiple disease episodes. Immunity acquired this way is mediated by IgG with specificity for parasite-encoded, clonally variant surface antigens (VSA) on the surface of infected erythrocytes (IEs). However, women in endemic areas become susceptible to P. falciparum infection when they become pregnant, particularly for the first time, regardless of previously acquired protective immunity. This conundrum was resolved when it was observed that the selective placental accumulation of IEs that characterizes pregnancy-associated malaria (PAM) is caused by an immunologically and functionally unique subset of VSA (VSAPAM) that is only expressed by parasites infecting pregnant women, and that protective immunity to PAM is mediated by IgG with specificity for VSAPAM. In this review we summarize the research leading to the identification of the distinctly structured PfEMP1 variant VAR2CSA as the dominant PAM-type VSA and as the clinically most important target of the protective immune response to placental P. falciparum infection.

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