Burkholderia vaccines: are we moving forward?

Abstract

The genus Burkholderia consists of diverse species which includes both “friends” and “foes.” Some of the “friendly” Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.

Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei

“…Therefore, the incorporation of antibody-inducing proteins is important when designing a subunit vaccine against Burkholderia. Nevertheless, it is currently understood that balanced cellular and humoral immune responses will be required for vaccine-induced protective immunity against B. pseudomallei and B. mallei (29,(36)(37)(38). Interestingly, in the present study, there does not appear to be a direct correlation between antibody titers (anti-LPS or antiprotein) and protection.…”

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

“…There has been significant effort in the past decade to devise vaccines for glanders and melioidosis, but many challenges remain, including considerable gaps in understanding immune mechanisms and correlates of protection, the availability of efficient vaccine delivery platforms, and the identification and characterization of protective antigens (57)(58)(59)(60)(61)(62)(63)(64). Given their important roles in pathogenicity, overall structure, and cellular location at the host-pathogen interface, autotransporter proteins (ATs) represent excellent targets for developing countermeasures (65)(66)(67)(68)(69)(70)(71)(72)(73)(74).…”

Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease

“…Recent work has shown that a vaccine would be a cost-effective intervention in Thailand if used in high-risk populations such as diabetics [10]. However, at present there is no available human vaccine, though a wide range of candidates including live attenuated mutants, killed cells, protein or polysaccharide sub-units and naked DNA vaccines have been tested in mice (for recent reviews see [11][12][13]). All of these vaccines are able to induce some protective immunity, protecting against the acute form of the disease.…”