Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Stålhammar‐Carlemalm, Margaretha; Waldemarsson, Johan; Johnsson, Eskil; Areschoug, Thomas; Lindahl, Gunnar

doi:10.1016/j.chom.2007.10.003

Cited by 38 publications

(50 citation statements)

References 31 publications

(64 reference statements)

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“…On the other hand, the immunogenic Alp1-specific site was most likely located in the N-terminal segment of Alp1, as some stretches of the bca and alp1 N termini showed considerable sequence divergencies, with the possibility of forming a structural basis for both the protein-specific epitope(s) and primer binding site(s) for both bca-and alp1-specific PCRs (6). These results have substantiated the assumption that both the repeat area and the N terminus of native Alp1 possess immunogenic sites, each site with distinctive specificity, similar to those of C␣ and R4 (Rib), demonstrated by immunization with recombinant constructs of stretches of the proteins (9,29). The location in the protein antigens of the Alp1/Alp2/Alp3 common site is not known with certainty, but location in the N termini seems likely.…”

Section: Discussionsupporting

confidence: 54%

“…An explanation for this could be that while the native Alp1-specific marker seemed to be immunodominant, a corresponding C␣-specific marker may be nonimmunodominant, an assumption supported by the results of other investigators (29). Thus, antisera raised against native C␣ or against other Alps tested for immunobiological function, including protective activity in experimental infections (14,21,28), may not have contained antibodies against N-terminal epitopes.…”

Section: Discussionmentioning

confidence: 52%

“…Thus, antisera raised against native C␣ or against other Alps tested for immunobiological function, including protective activity in experimental infections (14,21,28), may not have contained antibodies against N-terminal epitopes. Still such antisera were protective, which is conceivable, since recombinant constructs of both the C␣ N terminus and its repeat region induced protective antibodies on immunization (9,29).…”

Section: Discussionmentioning

confidence: 99%

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

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

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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....

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

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“…It was recently reported that nonimmunodominant regions were effective as building blocks in a streptococcal fusion protein vaccine (42). Although CAT and GBD were suggested to be nonimmunodominant in this study, they nevertheless may be attractive vaccine targets.…”

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confidence: 83%

Novel Epitopic Region of Glucosyltransferase B from Streptococcus mutans

Hoshino¹,

Kondô²,

Saito³

et al. 2011

Clin. Vaccine Immunol.

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In the development of a component vaccine against caries, the catalytic region (CAT) and glucan-binding domain (GBD) of glucosyltransferase B (GtfB) from Streptococcus mutans have been employed as target antigens. These regions were adopted as primary targets because they theoretically include epitopes associated with enzyme function. However, their antigenicities have not been fully evaluated. Although there are many reports about successful vaccination using these components, the principle has not yet been put to practical use. For these reasons, we came to doubt the effectiveness of the epitopes in vaccine production and reevaluated the antigenic region of GtfB by using in silico analyses combined with in vitro and in vivo experiments. The results suggested that the ca. 360-amino-acid variable region (VR) in the N terminus of GtfB is more reactive than CAT and GBD. This region is S. mutans and/or GtfB specific, nonconserved among other streptococcal Gtfs, and of unknown function. Immunization using an adenovirus vector-borne DNA vaccine confirmed that VR is an epitope that shows promise for the development of a caries vaccine.

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“…development and suggested the importance of analyzing major surface-exposed proteins for the presence of subregions that elicit protective immunity as a complement to the RV approach [65]. Additionally, the insolubility of many of the proteins tested by ELISA might also lead to false-negative titer-values, as it has been shown that linear epitopes are less likely to be immunodominant and elicit a good B-cell response if the protein possesses a higher-order structure [66].…”

Section: Discussionmentioning

confidence: 99%

In silico prediction of

Bager

Kudirkienė

Piedade

et al. 2014

Vet Res

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The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis and peritonitis in commercial egg-layers, leading to reduced egg production and increased mortality. Unfortunately, widespread multidrug resistance and antigenic diversity makes it difficult to control infections and novel prevention strategies are urgently needed. In this study, a pan-genomic reverse vaccinology (RV) approach was used to identify potential vaccine candidates. Firstly, the genomes of 10 selected Gallibacterium strains were analyzed and proteins selected on the following criteria; predicted surface-exposure or secretion, none or one transmembrane helix (TMH), and presence in six or more of the 10 genomes. In total, 42 proteins were selected. The genes encoding 27 of these proteins were successfully cloned in Escherichia coli and the proteins expressed and purified. To reduce the number of vaccine candidates for in vivo testing, each of the purified recombinant proteins was screened by ELISA for their ability to elicit a significant serological response with serum from chickens that had been infected with G. anatis. Additionally, an in silico prediction of the protective potential was carried out based on a protein property prediction method. Of the 27 proteins, two novel putative immunogens were identified; Gab_1309 and Gab_2312. Moreover, three previously characterized virulence factors; GtxA, FlfA and Gab_2156, were identified. Thus, by combining the pan-genomic RV approach with subsequent in vitro and in silico screening, we have narrowed down the pan-proteome of G. anatis to five vaccine candidates. Importantly, preliminary immunization trials indicated an in vivo protective potential of GtxA-N, FlfA and Gab_1309.

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Nonimmunodominant Regions Are Effective as Building Blocks in a Streptococcal Fusion Protein Vaccine

Cited by 38 publications

References 31 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

Novel Epitopic Region of Glucosyltransferase B from Streptococcus mutans

In silico prediction of

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