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.

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Microparticles (MPs) offer several advantages as unique vaccine delivery system, including the ease to manufacture, targeted delivery of antigen payload, sustained antigen release and possible role as an immuneadjuvant. In this study, we evaluated albumin matrix for pneumococcal (Pnc) serotype specific capsular polysaccharide (PS) antigen MPs. Microencapsulation of Pnc PS was successful with a product yield of >72%. The MP size, 1-5 μm, and negative zeta potential (-26.5 mV) were optimized to ensure effective-uptake and presentation of Pnc PS antigens to immune cells. In mice, ST 19F and 23F MPs exhibited >10-fold increase (P<0.01) in ST specific IgG response over PS in solution given with or without alum. Relatively higher immune response was observed for ST 6B MPs when compared to PS solution; however, ST6B PS solution along with alum resulted in an overall higher response when compared to ST6B MPs. Microencapsulation may offer a simple and effective mechanism for the immune-enhancement of poorly immunogenic antigens such as Pnc PS.