Immunization with a multiple antigen peptide containing defined B- and T-cell epitopes: production of bactericidal antibodies against group B Neisseria meningitidis

Christodoulides, Myron; Heckels, John E.

doi:10.1099/13500872-140-11-2951

Cited by 28 publications

(13 citation statements)

References 30 publications

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“…Porin proteins of gram-negative pathogens not only function as portals for nutrient acquisition across the outer membrane but have also been shown to play a role in pathogenesis by acting as adhesins (3,28) and targets of bactericidal antibodies (11,12,21,24). The conformation of these membrane-spanning proteins is believed to be particularly important to their biological function.…”

Section: Discussionmentioning

confidence: 99%

“…The conformation of these membrane-spanning proteins is believed to be particularly important to their biological function. Many surface-exposed epitopes on porins shown to be targets for bactericidal antibodies are, in fact, conformational (11,21). Thus, correct outer membrane protein conformation should be a key consideration in the study of porins as they relate to bacterial virulence and host immunity.…”

Section: Discussionmentioning

confidence: 99%

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Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure

et al. 1996

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. Here, we report the stable expression of recombinant Tromp1 (rTromp1) in Escherichia coli. rTromp1 expressed without its signal peptide and containing a 22-residue N-terminal fusion resulted in high-level accumulation of a nonexported soluble protein that was purified to homogeneity by fast protein liquid chromatography (FPLC). Specific antiserum generated to the FPLC-purified rTromp1 fusion identified on immunoblots of T. pallidum the native 31-kDa Tromp1 protein and two higher-molecular-mass oligomeric forms of Tromp1 at 55 and 80 kDa. rTromp1 was also expressed with its native signal peptide by using an inducible T7 promoter. Under these conditions, rTromp1 fractionated predominantly with the E. coli soluble and outer membrane fractions, but not with the inner membrane fraction. rTromp1 isolated from the E. coli outer membrane and reconstituted into planar lipid bilayers showed porin activity based on average singlechannel conductances of 0.4 and 0.8 nS in 1 M KCl. Whole-mount immunoelectron microscopy using infectionderived immune serum against T. pallidum indicated that rTromp1 was surface exposed when expressed in E. coli. These findings demonstrate that rTromp1 can be targeted to the E. coli outer membrane, where it has both porin activity and surface antigenic exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure

et al. 1996

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“…For instance, peptide vaccination has been successfully used to neutralize or protect against viruses (15,21,25,42), bacteria (10), and parasites (22). Based on data presented here, we propose peptide sequences of LF that are excellent candidates for a peptidebased vaccine for anthrax.…”

Section: Discussionmentioning

confidence: 99%

“…Although some B-cell epitopes are conformational in nature, others are comprised of a single continuous stretch of amino acids. The latter category of sequential epitopes is useful in rational design of peptide vaccines, and these epitopes have been demonstrated to elicit neutralizing or protective antibodies to viruses (15,21,25,42), bacteria (10), and parasites (22). Addition of key LF humoral epitopes to a recombinant PA vaccine is expected to increase the titers of LeTx-neutralizing antibodies in the sera of vaccinees and thus provide enhanced efficacy.…”

mentioning

confidence: 99%

Sequential B-Cell Epitopes ofBacillus anthracisLethal Factor Bind Lethal Toxin-Neutralizing Antibodies

et al. 2009

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The bipartite anthrax lethal toxin (LeTx) consisting of protective antigen (PA) and lethal factor (LF) is a major virulence factor contributing to death from systemic Bacillus anthracis infection. The current vaccine elicits antibodies directed primarily to PA; however, in experimental settings serologic responses to LF can neutralize LeTx and contribute to protection against infection. The goals of the present study were to identify sequential B-cell epitopes of LF and to determine the capacity of these determinants to bind neutralizing antibodies. Sera of recombinant LF-immunized A/J mice exhibited high titers of immunoglobulin G anti-LF reactivity that neutralized LeTx in vitro 78 days after the final booster immunization and protected the mice from in vivo challenge with 3 50% lethal doses of LeTx. These sera bound multiple discontinuous epitopes, and there were major clusters of reactivity on native LF. Strikingly, all three neutralizing, LF-specific monoclonal antibodies tested bound specific peptide sequences that coincided with sequential epitopes identified in polyclonal antisera from recombinant LF-immunized mice. This study confirms that LF induces high-titer protective antibodies in vitro and in vivo. Moreover, the binding of short LF peptides by LF-specific neutralizing monoclonal antibodies suggests that generation of protective antibodies by peptide vaccination may be feasible for this antigen. This study paves the way for a more effective anthrax vaccine by identifying discontinuous peptide epitopes of LF.

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“…This results in a large macromolecule with a unique three-dimensional configuration which has a high molar ratio of peptide antigen to core molecule and does not require a carrier protein for elicitation of the immune response. The MAP system has already been shown to be valuable in immunological studies of vaccine development in malaria and other systems (7,28,33,36,47).…”

mentioning

confidence: 99%

Immunogenicity of Well-Characterized SyntheticPlasmodium falciparumMultiple Antigen Peptide Conjugates

Joshi¹,

Gam²,

Boykins³

et al. 2001

Infect Immun

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Immunization with a multiple antigen peptide containing defined B- and T-cell epitopes: production of bactericidal antibodies against group B Neisseria meningitidis

Cited by 28 publications

References 30 publications

Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure

Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure

Sequential B-Cell Epitopes ofBacillus anthracisLethal Factor Bind Lethal Toxin-Neutralizing Antibodies

Immunogenicity of Well-Characterized SyntheticPlasmodium falciparumMultiple Antigen Peptide Conjugates

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