A Novel Innate Immune-Enhancement Strategy Combined with IVIG Rescues Mice from FatalStaphylococcus aureusSepticemia

Abstract

Staphylococcus aureus (SA) is a major community-acquired pathogen. The emergence of drug-resistant strains like, methicillin-resistant SA (MRSA), poses stiff challenges to therapeutic intervention. Passive immune-therapy with specific antibodies is being actively examined to treat fulminant infections with limited success. In this study, we demonstrate that P4, a 28-amino acid peptide, derived from pneumococcal surface adhesin A along with pathogen-specific antibody (IVIG; P4 therapy) is successful in enhancing the opsonophagocytic killing (OPK) of S. aureus in vitro. We questioned if it is possible to expand P4 therapy to treat staphylococcal infections in vivo. P4 therapy in combination with IVIG rescued 7/10 morbidly ill S. aureus-infected mice while only 2/10 survived in the control group.

IVIG-mediated protection against necrotizing pneumonia caused by MRSA

“…However, high-dose IVIG, 2 g/kg, is generally required for IVIG's anti-inflammatory effects, whereas protection in the rabbit model of necrotizing pneumonia was achieved using 1 / 10 of the human dose, 200 mg/kg. If there was an anti-inflammatory effect in the rabbit model, then it was likely to be minimal because 59 of 64 (92%) rabbits administered IVIG (200 mg The role of IVIG in enhancing in vitro opsonophagocytic killing of S. aureus has been debated (29)(30)(31)(32)(33). Notably, rabbits administered IVIG depleted of its antitoxin antibodies did not differ in lung bacterial counts from those treated with saline ( Fig.…”

Methicillin-Resistant Staphylococcus aureus in the Neonatal Intensive Care Unit

“…Research in academic centers, biotechnology, and pharmaceutical companies should focus on implementing a multidisciplinary approach for the development of new antibiotics against MRSA as strains resistant to current antibiotic regimens continue to emerge. 43 Additional treatment strategies, including innate immune-enhancement strategies 44 and genetic modulation of MRSA to restore antibiotic susceptibility, 45 that have already been explored in vitro and in vivo in animal models should be further evaluated as potential supplemental interventions for halting MRSA infections in human subjects. Finally, it is critical that medical communities continue to monitor and share reports regarding their local prevalence of MRSA strains, incidence of invasive MRSA infections, and MRSA antibiotic susceptibility patterns in an effort to provide cumulative data that can ultimately contribute to global awareness and treatment guidelines for this pervasive pathogen.…”

Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis

“…First, the opsonophagocytosis killing assay is an established and standardised method (29), widely used to compare phagocytic function in vaccine efficacy testing (30) and applied in previous work with P4 peptide (7,8,12,15).…”