Polysaccharide Specific Monoclonal Antibodies Provide Passive Protection against Intranasal Challenge with Burkholderia pseudomallei

David P Aucoin,Nicole L Marlenee,Alfredo G Torres,Richard A Bowen,Dana E Reed,Barbara M Judy,Thomas R Kozel,Peter Thorkildson,Paulo Lee Ho

doi:10.1371/journal.pone.0035386

Abstract

Burkholderia pseudomallei is a Gram-negative bacillus that is the causative agent of melioidosis. The bacterium is inherently resistant to many antibiotics and mortality rates remain high in endemic areas. The lipopolysaccharide (LPS) and capsular polysaccharide (CPS) are two surface-associated antigens that contribute to pathogenesis. We previously developed two monoclonal antibodies (mAbs) specific to the CPS and LPS; the CPS mAb was shown to identify antigen in serum and urine from melioidosis patients. The goal of this study was to determine if passive immunization with CPS and LPS mAbs alone and in combination would protect mice from a lethal challenge with B. pseudomallei. Intranasal (i.n.) challenge experiments were performed with B. pseudomallei strains 1026b and K96423. Both mAbs provided significant protection when administered alone. A combination of mAbs was protective when low doses were administered. In addition, combination therapy provided a significant reduction in spleen colony forming units (cfu) compared to results when either the CPS or LPS mAbs were administered alone.

Highlights

Melioidosis occurs primarily in the tropics and is caused by the soil dwelling pathogen B. pseudomallei
By Western blot monoclonal antibodies (mAbs) 4C7 produces a ladder pattern typical of B. pseudomallei LPS binding [22,23,24,25] and mAb 3C5 is reactive with purified capsular polysaccharide (CPS) that was structurally verified by nuclear magnetic resonance (NMR) [17]
The initial passive immunization study consisted of i.p. administration of 1 mg of mAb 3C5 or 4C7 alone and 1 mg of each mAb in combination; these doses did not cause any adverse effects in the mice

Summary

Introduction

Melioidosis occurs primarily in the tropics and is caused by the soil dwelling pathogen B. pseudomallei. Recommended treatment with effective antibiotics is intensive, consisting of a short parenteral phase followed by a long oral phase [4]. A recent prospective study determined that the incidence of melioidosis has increased in northeast Thailand from 1997–2006 and the mortality rate during this period was nearly 43% [6]. In the same geographical region, melioidosis is the third most common cause of death from infectious disease after acquired immunodeficiency syndrome (AIDS) and tuberculosis [6]. In regions of northern Australia, where intensive care treatment is more readily available, the mortality rate is still alarmingly high at 20% [2,7]

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