Background:
Extremely drug-resistant (XDR)
Acinetobacter baumannii
is a notorious and frequently encountered pathogen demanding novel therapeutic interventions. An initial monoclonal antibody (MAb), C8, raised against
A. baumannii
capsule proved a highly effective treatment against a minority of clinical isolates. To overcome this limitation, we broadened coverage by developing a second antibody for use in a combination regimen.
Methods:
We sought to develop an additional anti-
A. baumannii
MAb through hybridoma technology by immunizing mice with sublethal inocula of virulent, XDR clinical isolates not bound by MAb C8.
Results:
We identified a new antibacterial MAb, 65, which bound to strains in a pattern distinct from and complementary to MAb C8. MAb 65 enhanced macrophage opsonophagocytosis of targeted strains and markedly improved survival in lethal bacteremic sepsis and aspiration pneumonia murine models of
A. baumannii
infection. MAb 65 was also synergistic with colistin, substantially enhancing protection compared to monotherapy. Treatment with MAb 65 significantly reduced blood bacterial density, ameliorated cytokine production (IL-1β, IL-6, IL-10, and TNF), and sepsis biomarkers.
Conclusions:
We describe a novel MAb targeting
A. baumannii
that broadens immunotherapeutic strain coverage, is highly potent and effective, and synergistically improves outcomes in combination with antibiotics.
Acinetobacter baumannii
is an extremely drug-resistant pathogen necessitating the development of new therapies. We seek to generate a cocktail of monoclonal antibodies (MAbs) that can target the full diversity of
A. baumannii
isolates.
Recently, we reported rifabutin hyper-activity against Acinetobacter baumannii. We sought to characterize if any additional rifamycins (n = 22) would also display hyper-activity when tested in iron-limited media against A. baumannii, K. pneumoniae, and E. coli. MICs were determined against representative clinical isolates using the iron-limited media RPMI-1640. Only rifabutin was hyperactive against A. baumannii.
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