Anti-lipoteichoic acid monoclonal antibody (pagibaximab) studies for the prevention of staphylococcal bloodstream infections in preterm infants

Abstract

These studies demonstrated safety and tolerability of pagibaximab with no observed reduction in sepsis. Reported adverse events in both treatment and placebo groups were similar and consistent with events commonly observed in VLBW infants. Antistaphylococcal immunoglobulins alone have been unsuccessful in preventing nosocomial infections. Further investigations need to evaluate any potential immunomodulating products in preterm animal models prior to human studies. Future studies are required to determine how to best augment the immature immune system, likely through the use of multiple immunomodulating agents to successfully prevent infections in preterm infants.

Potent human antibodies against SpA5 identified by high-throughput single-cell sequencing of phase I clinical volunteers’ B cells

“…Antibodies are effective drugs to neutralize bacterial toxins and can provide timely treatment for infected patients, which is valuable for in-depth research. 9 In recent years, the antibody drugs Veronate 17 , 18 and tefibazumab 19 , 20 , 21 , 22 , 23 targeting ClfA, pagibaximab 24 , 25 , 26 targeting lipophosphatidylcholic acid, and Aurograb 27 , 28 targeting cell membrane proteins were terminated with failure after entering the clinical evaluation. On the other hand, human mAb MEDI4893 and human mAb AR-301, antibody drugs targeting hemolysin and two-component toxins, and Altastaph, an antibody drug targeting podocarp polysaccharides, all showed better results in the clinical evaluations and entered into the next step of clinical evaluation.…”

Potent human antibodies against SpA5 identified by high-throughput single-cell sequencing of phase I clinical volunteers’ B cells

“…Antibodies are effective drugs to neutralize bacterial toxins and can provide timely treatment for infected patients, which is valuable for in-depth research. 9 In recent years, the antibody drugs Veronate 17 , 18 and tefibazumab 19 , 20 , 21 , 22 , 23 targeting ClfA, pagibaximab 24 , 25 , 26 targeting lipophosphatidylcholic acid, and Aurograb 27 , 28 targeting cell membrane proteins were terminated with failure after entering the clinical evaluation. On the other hand, human mAb MEDI4893 and human mAb AR-301, antibody drugs targeting hemolysin and two-component toxins, and Altastaph, an antibody drug targeting podocarp polysaccharides, all showed better results in the clinical evaluations and entered into the next step of clinical evaluation.…”

Biofilms in Periprosthetic Joint Infections: A Review of Diagnostic Modalities, Current Treatments, and Future Directions

“…Pagibaximab, a monoclonal antibody targeting lipotechoic acid which is a component of the bacterial cell wall, was designed for the treatment of S. epidermidis biofilm associated sepsis, especially in neonates, but failed to show a reduction in Staphylococcal sepsis. 79 These results suggest that immunologic therapy may need to be used in conjunction with other therapies, and requires further investigation in PJI models prior to clinical implementation, especially given the high prevalence of Staphylococcal PJI.…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…Although monoclonal antibodies effectively block QS signalling among pathogenic bacterial species, their applications for treating bacterial infections are still in the initial stage [ 260 ]. Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ].…”

“…Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ]. Nevertheless, several interesting S. aureus vaccine candidates have shown promising results in pre-clinical studies [ 265 , 266 ].…”

Potent human antibodies against SpA5 identified by high-throughput single-cell sequencing of phase I clinical volunteers’ B cells

“…Antibodies are effective drugs to neutralize bacterial toxins and can provide timely treatment for infected patients, which is valuable for in-depth research. 9 In recent years, the antibody drugs Veronate 17 , 18 and tefibazumab 19 , 20 , 21 , 22 , 23 targeting ClfA, pagibaximab 24 , 25 , 26 targeting lipophosphatidylcholic acid, and Aurograb 27 , 28 targeting cell membrane proteins were terminated with failure after entering the clinical evaluation. On the other hand, human mAb MEDI4893 and human mAb AR-301, antibody drugs targeting hemolysin and two-component toxins, and Altastaph, an antibody drug targeting podocarp polysaccharides, all showed better results in the clinical evaluations and entered into the next step of clinical evaluation.…”

Biofilms in Periprosthetic Joint Infections: A Review of Diagnostic Modalities, Current Treatments, and Future Directions

“…Pagibaximab, a monoclonal antibody targeting lipotechoic acid which is a component of the bacterial cell wall, was designed for the treatment of S. epidermidis biofilm associated sepsis, especially in neonates, but failed to show a reduction in Staphylococcal sepsis. 79 These results suggest that immunologic therapy may need to be used in conjunction with other therapies, and requires further investigation in PJI models prior to clinical implementation, especially given the high prevalence of Staphylococcal PJI.…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…Although monoclonal antibodies effectively block QS signalling among pathogenic bacterial species, their applications for treating bacterial infections are still in the initial stage [ 260 ]. Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ].…”

“…Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ]. Nevertheless, several interesting S. aureus vaccine candidates have shown promising results in pre-clinical studies [ 265 , 266 ].…”

Potent human antibodies against SpA5 identified by high-throughput single-cell sequencing of phase I clinical volunteers’ B cells

“…Antibodies are effective drugs to neutralize bacterial toxins and can provide timely treatment for infected patients, which is valuable for in-depth research. 9 In recent years, the antibody drugs Veronate 17 , 18 and tefibazumab 19 , 20 , 21 , 22 , 23 targeting ClfA, pagibaximab 24 , 25 , 26 targeting lipophosphatidylcholic acid, and Aurograb 27 , 28 targeting cell membrane proteins were terminated with failure after entering the clinical evaluation. On the other hand, human mAb MEDI4893 and human mAb AR-301, antibody drugs targeting hemolysin and two-component toxins, and Altastaph, an antibody drug targeting podocarp polysaccharides, all showed better results in the clinical evaluations and entered into the next step of clinical evaluation.…”

Biofilms in Periprosthetic Joint Infections: A Review of Diagnostic Modalities, Current Treatments, and Future Directions

“…Pagibaximab, a monoclonal antibody targeting lipotechoic acid which is a component of the bacterial cell wall, was designed for the treatment of S. epidermidis biofilm associated sepsis, especially in neonates, but failed to show a reduction in Staphylococcal sepsis. 79 These results suggest that immunologic therapy may need to be used in conjunction with other therapies, and requires further investigation in PJI models prior to clinical implementation, especially given the high prevalence of Staphylococcal PJI.…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…Although monoclonal antibodies effectively block QS signalling among pathogenic bacterial species, their applications for treating bacterial infections are still in the initial stage [ 260 ]. Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ].…”

“…Several antibodies, including ClfA, CP5 and 8, PNAG, Hla, and HlgAB targeting S. aureus biofilm, have been tested as passive vaccines in clinical phase II and/or III trials [ 261 , 262 , 263 ]. However, none of them improved the clinical outcome in treating bacteremia and cystic fibrosis patients [ 261 , 262 , 263 , 264 ]. Nevertheless, several interesting S. aureus vaccine candidates have shown promising results in pre-clinical studies [ 265 , 266 ].…”