Bacteriophage T4 Capsid: A Unique Platform for Efficient Surface Assembly of Macromolecular Complexes

Li, Qin; Shivachandra, Sathish Bhadravati; Leppla, Stephen H.; Rao, Venigalla B.

doi:10.1016/j.jmb.2006.08.049

Cited by 43 publications

(54 citation statements)

References 41 publications

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“…Recent data show that antigens fused to Soc can be efficiently displayed on T4 [Li et al, unpublished results]. Display can be amplified by adding either short epitopes or large complexes through interaction with the first "layer" of displayed antigens [37]. Further enhancement of immune responses can be achieved through display of targeting molecule(s) and/or incorporating expressible genes into phage T4 genome.…”

Section: Discussionmentioning

confidence: 99%

Multicomponent anthrax toxin display and delivery using bacteriophage T4

Shivachandra

Peachman

et al. 2007

Vaccine

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We describe a multicomponent antigen display and delivery system using bacteriophage T4. Two dispensable outer capsid proteins, Hoc (highly antigenic outer capsid protein, 155 copies) and Soc (small outer capsid protein, 810 copies), decorate phage T4 capsid. These proteins bind to the symmetrically localized capsid sites, which appear following prohead assembly and expansion. We hypothesized that multiple antigens fused to Hoc can be displayed on the same capsid and such particles can elicit broad immunological responses. Anthrax toxin proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF), and their functional domains, were fused to Hoc with an N-terminal hexa-histidine tag and the recombinant proteins were over-expressed in E. coli and purified. Using a defined in vitro assembly system, the anthrax-Hoc fusion proteins were efficiently displayed on T4 capsid, either individually or in combinations. All of the 155 Hoc binding sites can be occupied by one antigen, or they can be split among two or more antigens by varying their molar ratio in the binding reaction. Immunization of mice with T4 phage carrying PA, LF, and EF elicited strong antigen-specific antibodies against all antigens as well as lethal toxin neutralization titers. The triple antigen T4 phage elicited stronger PA-specific immune responses than the phage displaying PA alone. These features offer novel avenues to develop customized multicomponent vaccines against anthrax and other pathogenic diseases.

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Section: Discussionmentioning

confidence: 99%

Multicomponent anthrax toxin display and delivery using bacteriophage T4

Shivachandra

Peachman

et al. 2007

Vaccine

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“…Both Hoc and Soc are dispensable for capsid assembly and bind to the assembled capsid in the last stage of its maturation (18). These proteins have been used as a platform for display of pathogenic antigens on the capsid surface (12,20,29,35,40). Soc helps to stabilize the T4 capsid against extremes of pH and temperature (18,34,42).…”

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confidence: 99%

Structure of the Three N-Terminal Immunoglobulin Domains of the Highly Immunogenic Outer Capsid Protein from a T4-Like Bacteriophage

Fokine

Islam

Zhang

et al. 2011

J Virol

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105

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The head of bacteriophage T4 is decorated with 155 copies of the highly antigenic outer capsid protein (Hoc). One Hoc molecule binds near the center of each hexameric capsomer. Hoc is dispensable for capsid assembly and has been used to display pathogenic antigens on the surface of T4. Here we report the crystal structure of a protein containing the first three of four domains of Hoc from bacteriophage RB49, a close relative of T4. The structure shows an approximately linear arrangement of the protein domains. Each of these domains has an immunoglobulin-like fold, frequently found in cell attachment molecules. In addition, we report biochemical data suggesting that Hoc can bind to Escherichia coli, supporting the hypothesis that Hoc could attach the phage capsids to bacterial surfaces and perhaps also to other organisms. The capacity for such reversible adhesion probably provides survival advantages to the bacteriophage.

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“…The bacteriophage T4 display provides a simple yet powerful strategy to convert soluble antigens into nano-particulate antigens by attaching Soc to one end of the antigen (66,67). We previously showed that such nanoparticles displaying HIV-1 Gag p24 and other antigens induced strong Ab as well as cellular responses (67,68).…”

Section: Discussionmentioning

confidence: 99%

Designing a Soluble Near Full-length HIV-1 gp41 Trimer

Gao

Wieczorek

Peachman

et al. 2013

Journal of Biological Chemistry

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Background:The envelope glycoprotein gp41 is a key component of HIV-1 virus entry into host cells. Results: Structure-based mutagenesis and biochemical approaches lead to the design of soluble gp41 trimers. Conclusion: Trimers are in a prehairpin structure, similar to that observed during virus entry. Significance: The new gp41 recombinants could lead to the development of novel diagnostics, therapeutics, and vaccines.

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Bacteriophage T4 Capsid: A Unique Platform for Efficient Surface Assembly of Macromolecular Complexes

Cited by 43 publications

References 41 publications

Multicomponent anthrax toxin display and delivery using bacteriophage T4

Multicomponent anthrax toxin display and delivery using bacteriophage T4

Structure of the Three N-Terminal Immunoglobulin Domains of the Highly Immunogenic Outer Capsid Protein from a T4-Like Bacteriophage

Designing a Soluble Near Full-length HIV-1 gp41 Trimer

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