Prevention of Staphylococcus aureus Infections by Glycoprotein Vaccines Synthesized in Escherichia coli

Wacker, Michael; Wang, Linhui; Kowarik, Michael; Dowd, Meghan; Lipowsky, Gerd; Faridmoayer, Amir; Shields, Kelly; Park, Saeyoung; Alaimo, Cristina; Kelley, Kathryn; Braun, Martin; Quebatte, Julien; Gambillara, Veronica; Carranza, Paula; Steffen, Michael; Lee, Jean C.

doi:10.1093/infdis/jit800

Cited by 115 publications

(111 citation statements)

References 40 publications

(57 reference statements)

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“…17,24,25,38 Antibodies to CPs neutralize the antiphagocytic nature of the capsule and effectively mediate uptake and killing by professional phagocytes. Passive immunization with CP5 or CP8 antibodies has shown protection in rodent models of mastitis, bacteremia, endocarditis, and skin abscesses.…”

Section: Discussionmentioning

confidence: 99%

“…25,[39][40][41] Despite their failure in clinical trials when used alone in hemodialysis patients, 42,43 CP5 and CP8 conjugate vaccines are thought to be important components in a multivalent staphylococcal vaccine. 1,25,38,44 Because diverse S. aureus clinical isolates (both methicillin-sensitive and -resistant) produce surface-associated CP5 or CP8, 14,15,37 we considered that mAbs to CP5 or CP8 with opsonic activity might be included in a mAb cocktail to prevent or reduce staphylococcal bacteremia. S. aureus USA300, which is highly prevalent in the United States, does not produce a capsule and thus would not be a target for mAbs against CP5 or CP8.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26] To determine whether the CP5-and CP8-specific mAbs were functionally opsonic, we performed in vitro OPK assays with agar-grown S. aureus and serial dilutions of either a purified backbone-specific or O-acetyl-specific mAb. Opsonic activity was compared by determining the mAb concentration that yielded 50% killing of the bacterial inoculum.…”

Section: Opsonophagocytic Killing (Opk) Of S Aureus Mediated By Mabsmentioning

confidence: 99%

“…25,26 Therefore, the CP5 backbone specific mAb 4C2 was evaluated for its ability to protect mice against bacteremia in passive immunization experiments. As shown in Fig.…”

Section: Opsonophagocytic Killing (Opk) Of S Aureus Mediated By Mabsmentioning

confidence: 99%

“…aureus clearance by the host is dependent upon opsonic antibodies that promote uptake and killing of this microbe by host neutrophils. Antibodies to S. aureus CP5 and CP8 are particularly effective in promoting opsonophagocytic killing of S. aureus [24][25][26] and reducing bacteremia in a murine infection model., 25,26 In this report we evaluate mAbs against S. aureus CP5 and CP8 for their specificity in binding to a wide variety of encapsulated clinical isolates and their ability to mediate in vitro opsonophagocytic bacterial killing. We assessed protection against bacteremia provoked by both serotype 5 and 8 S. aureus, and we discovered that serotype 8 S. aureus clinical isolates release soluble CP8 during culture and infection.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

et al. 2016

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The capsular polysaccharide (CP) produced by Staphylococcus aureus is a virulence factor that allows the organism to evade uptake and killing by host neutrophils. Polyclonal antibodies to the serotype 5 (CP5) and type 8 (CP8) capsular polysaccharides are opsonic and protect mice against experimental bacteremia provoked by encapsulated staphylococci. Thus, passive immunotherapy using CP antibodies has been considered for the prevention or treatment of invasive antibioticresistant S. aureus infections. In this report, we generated monoclonal antibodies (mAbs) against S. aureus CP5 or CP8. Backbone specific mAbs reacted with native and O-deacetylated CPs, whereas Oacetyl specific mAbs reacted only with native CPs. Reference strains of S. aureus and a selection of clinical isolates reacted by colony immunoblot with the CP5 and CP8 mAbs in a serotype-specific manner. The mAbs mediated in vitro CP type-specific opsonophagocytic killing of S. aureus strains, and mice passively immunized with CP5 mAbs were protected against S. aureus bacteremia. Neither CP8-specific mAbs or polyclonal antibodies protected mice against bacteremia provoked by serotype 8 S. aureus clinical isolates, although these same antibodies did protect against a serotype 5 S. aureus strain genetically engineered to produce CP8. We detected soluble CP8 in culture supernatants of serotype 8 clinical isolates and in the plasma of infected animals. Serotype 5 S. aureus released significantly less soluble CP5 in vitro and in vivo. The release of soluble CP8 by S. aureus may contribute to the inability of CP8 vaccines or antibodies to protect against serotype 8 staphylococcal infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Opsonophagocytic Killing (Opk) Of S Aureus Mediated By Mabsmentioning

confidence: 99%

“…25,26 Therefore, the CP5 backbone specific mAb 4C2 was evaluated for its ability to protect mice against bacteremia in passive immunization experiments. As shown in Fig.…”

Section: Opsonophagocytic Killing (Opk) Of S Aureus Mediated By Mabsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

et al. 2016

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Antibacterial Carbohydrate Vaccines

Compostella,

Morelli,

Lay

2023

Carbohydrate‐Based Therapeutics

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Developing an Effective Glycan‐Based Vaccine for Streptococcus Pyogenes

2022

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Streptococcus pyogenes is a primary infective agent that causes approximately 700 million human infections each year, resulting in more than 500 000 deaths. Carbohydrate‐based vaccines are proven to be one of the most promising subunit vaccine candidates, as the bacterial glycan pattern(s) are different from mammalian cells and show increased pathogen serotype conservancy than the protein components. In this Review we highlight reverse vaccinology for use in the development of subunit vaccines against S. pyogenes, and report reproducible methods of carbohydrate antigen production, in addition to the structure–immunogenicity correlation between group A carbohydrate epitopes and alternative vaccine antigen carrier systems. We also report recent advances used to overcome hurdles in carbohydrate‐based vaccine development.

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Prevention of Staphylococcus aureus Infections by Glycoprotein Vaccines Synthesized in Escherichia coli

Abstract: Glycoengineering technology, whereby polysaccharide and protein antigens are enzymatically linked in a simple E. coli production system, has broad applicability for use in vaccine development against encapsulated microbial pathogens.

Cited by 115 publications

References 40 publications

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

Antibacterial Carbohydrate Vaccines

Developing an Effective Glycan‐Based Vaccine for Streptococcus Pyogenes

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