Recombinant Group B<i>Streptococcus</i>Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein

Yang, Haw; Mascuch, Samantha J.; Madoff, Lawrence C.; Paoletti, Lawrence C.

doi:10.1128/cvi.00030-08

Cited by 17 publications

(18 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Theoretically, a two-component vaccine composed, for instance, of the C␣ and R4/Rib repeat regions might induce increased resistance against all of these isolates. The results of other studies have supported this possibility (29,33).…”

Section: Discussionsupporting

confidence: 79%

“…For instance, R4/Rib and Alp3 have nearly identical repeat units with immunological cross-reactivity, including cross-protection against infection in animal models (27,33), while the Alp3 and R4/Rib N termini, which showed 59% homology (15), were immunologically divergent (17,18). The R4/Rib N terminus seems to be R4/Rib specific immunologically (18), while the Alp3 N terminus is identical to the Alp2 N terminus, with respect to sequence (12) and immunological specificity (17).…”

Section: Discussionmentioning

confidence: 99%

“…The structural arrangement provides for protein-specific immune reactions in some cases and variable immunological crossreactivities between the proteins. Epitopes of the Alps induce antibodies which protect against GBS infection in experimental models, including cross-protection by cross-reacting antibodies (1,12,15,27,33).The C␣-encoding gene bca was the first Alp gene sequenced (GenBank accession no. M97256) (22), and C␣ has been studied extensively.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

Most isolates of group B streptococci (GBS) express an alpha-like protein (Alp), C␣ (encoded by bca), Alp1 (also called epsilon; alp1), Alp2 (alp2), Alp3 (alp3), Alp4 (alp4), or R4/Rib (rib). These proteins are chimeras with a mosaic structure and with antigenic determinants with variable immunological crossreactivities between the Alps, including Alp1 and C␣ cross-reactivity. This study focused on antigenic domains of Alp1, studied by using rabbit antisera in immunofluorescence, Western blotting, and enzymelinked immunosorbent assay (ELISA)-based tests and whole cells of GBS or trypsin-extracted and partially purified antigens from the strains A909 (serotype Ia/C␣, C␤) and 335 (Ia/Alp1). Alp1 and C␣ shared an antigenic determinant, Alp1/C␣ common, not harbored by other Alps, probably located in the Alp1 and C␣ repeat units, as these units are nearly identical in genomic sequence. An antigenic Alp1 determinant was Alp1 specific and was most likely located in the N-terminal unit of Alp1 in which an Alp1-specific primer site for PCR is also located. In addition, Alp1 possessed a domain with low immunogenicity which cross-reacted immunologically with Alp2 and Alp3, with unknown location in Alp1. Alp1 was partially degraded by trypsin during antigen extraction but with the antigenic domains preserved. The results indicate that C␣ and Alp1 are immunologically related in the same manner that R4 (Rib) and Alp3 are related. The domain called Alp1 specific should be important in GBS serotyping as a surface-anchored serosubtype marker. The Alp1/C␣ common determinant may be of prime interest as an immunogenic domain in a GBS vaccine.Group B streptococci (GBS) can be classified into 10 serotypes based on the capsular polysaccharides (CPS), serotypes Ia, Ib, and II through IX. In addition, a number of surfaceanchored and strain-variable protein antigens enable serosubtyping of GBS, resulting in a large number of GBS serovariants. For example, 25 different serovariants were identified in a GBS strain collection from Zimbabwe (19). The surfacelocalized proteins include C␤ encoded by bac, C␣ (bca), the alpha-like proteins (Alps) Alp1 (alp1; also called epsilon), Alp2 (alp2), Alp3 (alp3), Alp4 (alp4), R4/Rib (rib), the GBS protective protein R5 (sar5) (8), the R3 protein (11, 32), and a recently described novel protein called Z (20). Neither R3 nor Z has as yet been sequenced. The Alps are chimeras with a mosaic structure composed of an N terminus with 220 to 230 amino acids (aa), including the signal sequence (6), an area with a variable number of identical, tandem repeats, each containing ϳ80 aa, and a C terminus (12,15,22,31). The structural arrangement provides for protein-specific immune reactions in some cases and variable immunological crossreactivities between the proteins. Epitopes of the Alps induce antibodies which protect against GBS infection in experimental models, including cross-protection by cross-reacting antibodies (1,12,15,27,33).The C␣-encoding gene bca was the first Alp gene sequenced (GenBank accession no....

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

show abstract

“…these proteins can be considered vaccine candidates, either alone or as carrier proteins coupled to CPS (33,34).…”

mentioning

confidence: 99%

Putative Novel Surface-Exposed Streptococcus agalactiae Protein Frequently Expressed by the Group B Streptococcus from Zimbabwe

Mavenyengwa

Mæland

Moyo

2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

Group B streptococci (GBS) express a variety of surface-exposed and strain-variable proteins which function as phenotypic markers and as antigens which are able to induce protective immunity in experimental settings. Among these proteins, the chimeric and immunologically cross-reacting alpha-like proteins are particularly important. Another protein, R3, which has been less well studied, occurred at a frequency of 21.5% in GBS from Zimbabwe and, notably, occurred in serotype V strains at a frequency of 75.9%. Working with rabbit antiserum raised against the R3 reference strain ATCC 49447 (strain 10/84; serotype V/R3) to detect the expression of the R3 protein, we recorded findings which suggested that strain 10/84 expressed a strain-variable protein antigen, in addition to R3. The antigen was detected by various enzyme-linked immunosorbent assay-based tests by using acid extract antigens or GBS whole-cell coats and by whole-cell-based Western blotting. We named the putative novel antigen the Z antigen. The Z antigen was a high-molecular-mass antigen that was susceptible to degradation by pepsin and trypsin but that was resistant to m-periodate oxidation and failed to show immunological cross-reactivity with any of a variety of other GBS protein antigens. The Z antigen was expressed by 33/121 (27.2%) of strains of a Zimbabwean GBS strain collection and by 64.2% and 72.4% of the type Ib and type V strains, respectively, and was occasionally expressed by GBS of other capsular serotypes. Thus, the putative novel GBS protein named Z showed distinct capsular antigen associations and presented as an important phenotypic marker in GBS from Zimbabwe. It may be an important antigen in GBS from larger areas of southern Africa. Its prevalence in GBS from Western countries is not known.Streptococcus agalactiae (the group B streptococcus [GBS]) possesses genotypic and phenotypic markers which are important in epidemiological settings. Among the established phenotypic markers, the capsular polysaccharides (CPSs) Ia, Ib, and II through IX play prominent roles in the classification of GBS, in the pathogenesis of GBS disease, and as targets of protective antibodies (15). A variety of surface-anchored and strain-variable proteins are also important GBS markers. These proteins make it possible to define GBS serosubtypes within each CPS type by using antibody-based or gene-based methods for subtyping (6, 11 19, 22). These proteins include Cß and the alpha-like proteins (Alps) C␣, Alp1 (formerly epsilon), Alp2 and Alp3 (formerly probably R1), and Rib (another designation for the R4 protein) (28). The Alps are characterized, among other ways, by a repeat-containing region which has a causal relation to the ladder-like patterns formed by these proteins on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and Western blotting. The Alps possess chimeric sequences, show variable immunological crossreactivities, and induce increased resistance to GBS infections in experimental models (1,13,15,18,30). For this reason, th...

show abstract

“…It remains to be seen whether more refined immunological techniques will result in detection of an Alp3-specific antigenic marker. Due to its cross-reactivity with other Alps, Alp3 may be of considerable interest as a vaccine candidate in a CPS/Alp3 conjugate vaccine, as a free protein, or as a recombinant version of antigenic Alp3 domains (36). A summary of immunological characteristics of Alp2 and Alp3 is included in Fig.…”

Section: Fig 2 Schematic Presentation Of the Immunodominant Domains Omentioning

confidence: 99%

Survey of Immunological Features of the Alpha-Like Proteins of Streptococcus agalactiae

Mæland

Afset

Lyng

et al. 2014

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

bNearly all Streptococcus agalactiae (group B streptococcus [GBS]) strains express a protein which belongs to the so-called alphalike proteins (Alps), of which C␣, Alp1, Alp2, Alp3, Rib, and Alp4 are known to occur in GBS. The Alps are chimeras which form mosaic structures on the GBS surface. Both N-and C-terminal stretches of the Alps possess immunogenic sites of dissimilar immunological specificity. In this review, we have compiled data dealing with the specificity of the N-and C-terminal immunogenic sites of the Alps. The majority of N-terminal sites show protein specificity while the C-terminal sites show broader cross-reactivity. Molecular serotyping has revealed that antibody-based serotyping has often resulted in erroneous Alp identification, due to persistence of cross-reacting antibodies in antisera for serotyping. Retrospectively, this could be expected on the basis of sequence analysis results. Some of the historical R proteins are in fact Alps. The data included in the review may provide a basis for decisions regarding techniques for the preparation of specific antisera for serotyping of GBS, for use in other approaches in GBS research, and for decision making in the context of GBS vaccine developments.

show abstract

Recombinant Group BStreptococcusAlpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein

Cited by 17 publications

References 47 publications

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Putative Novel Surface-Exposed Streptococcus agalactiae Protein Frequently Expressed by the Group B Streptococcus from Zimbabwe

Survey of Immunological Features of the Alpha-Like Proteins of Streptococcus agalactiae

Contact Info

Product

Resources

About