Protection against Experimental Melioidosis following Immunization with Live Burkholderia thailandensis Expressing amanno-Heptose Capsule

Abstract

cMelioidosis is a severe infectious disease caused by Burkholderia pseudomallei. It is highly resistant to antibiotic treatment, and there is currently no licensed vaccine. Burkholderia thailandensis is a close relative of Burkholderia pseudomallei but is essentially avirulent in mammals. In this report, we detail the protective efficacy of immunization with live B. thailandensis E555, a strain which has been shown to express an antigenic capsule similar to that of B. pseudomallei. Immunization with E555 induced significant protection against a lethal intraperitoneal B. pseudomallei challenge in a mouse model of infection, with no mice succumbing to infection over the course of the study, even with challenges of up to 6,000 median lethal doses. By comparison, mice immunized with B. thailandensis not expressing a B. pseudomallei-like capsule had significantly decreased levels of protection. E555-immunized mice had significantly higher levels of IgG than mice immunized with noncapsulated B. thailandensis, and these antibody responses were primarily directed against the capsule.

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

“…While the constitutively expressed capsule and LPS are lead vaccine targets for B. mallei and B. pseudomallei (110)(111)(112)(113)(114), the results of our passive-transfer experiments with adsorbed immune serum demonstrate the protective value of antigens selectively expressed in vivo during vaccination with the batA KO mutant. The data show that a single dose of immune serum depleted of antibodies binding to whole B. mallei bacteria cultured in vitro provides significant protection against lethal challenge during acute and chronic infection (Fig.…”

“…The ELISA data in Fig. S5 in the supplemental material demonstrate that this treatment effectively removed antibodies against antigens constitutively expressed in vitro, including capsular polysaccharides and LPS, which are the most abundant molecules on the surface of the organism and lead targets for vaccine development in the field (110)(111)(112)(113)(114). Remarkably, the adsorbed serum, which was completely depleted of antibodies binding to laboratory-grown bacteria, retained the ability to protect against lethal aerosol exposure to WT B. mallei ATCC 23344 at a level that was comparable to that of IgG antibodies purified from whole immune serum ( Fig.…”

Burkholderia pseudomallei Capsular Polysaccharide Conjugates Provide Protection against Acute Melioidosis

“…After clotting at 4°C, the serum was removed and stored at Ϫ20°C until required for use. Responses directed against the OPS, CPS, or LolC antigen were assessed by an enzyme-linked immunosorbent assay (ELISA) essentially as previously described (40). A reading of twice the background or higher was considered positive, and the titer was determined to be the reciprocal of the final positive dilution.…”

Vaccines for the Prevention of Melioidosis and Glanders

“…LAV candidates targeting various virulence factors have also been prepared and evaluated; however, all have failed to demonstrate sterilizing immunity against long-term infections, which are typically observed 30 days post-challenge [23, 41]. In addition to the economic burden associated with designing and manufacturing LAVs, there are significant safety concerns due to the ability of attenuated pathogens to transform into virulent strains, limiting therapeutic opportunities for elderly (>65 years) and immunocompromised individuals [42].…”