Consensus on the Development of Vaccines against Naturally Acquired Melioidosis

Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to select and advance candidates for testing in relevant nonhuman primate models and in human clinical trials.Development of such a vaccine was the topic of a meeting in the United Kingdom in March 2014 attended by international candidate vaccine developers, researchers, and government health officials.The focus of the meeting was advancement of vaccines for prevention of natural infection, rather than for protection from the organism's known potential for use as a biological weapon.A direct comparison of candidate vaccines in well-characterized mouse models was proposed.Knowledge gaps requiring further research were identified.Recommendations were made to accelerate the development of an effective vaccine against melioidosis.M elioidosis vaccines are urgently needed for both pub- lic health and biodefense purposes.The bacterium Burkholderia pseudomallei, the causal organism of melioidosis, was designated as a category B select agent by the US Centers for Disease Control and Prevention (CDC) and as a Tier 1 select agent by National Select Agent Registry (NASR), a joint program of the CDC and the Animal and Plant Health Inspection Service of the US Department of Agriculture.These designations have led to considerable research funding to develop a melioidosis vaccine (1,2).The potential for humans to be infected with B. pseudomallei by inhalation, the low infective dose by this route, and difficulties associated with diagnosis and treatment have led to this organism being considered to be at high risk for deliberate misuse as a weapon (3,4,5).B. pseudomallei is readily isolated from soil and water in many tropical areas across Southeast Asia, the Indian subcontinent, northern Australia, and parts of South America and the Caribbean (6).In these areas, melioidosis can be naturally acquired by skin inoculation, ingestion, and inhalation of environmental B. pseudomallei.In northeast Thailand, melioidosis kills an estimated >1,000 persons per year (7).A vaccine could be cost-effective for the prevention of melioidosis among populations at high risk for infection by B. pseudomallei, such as persons who have diabetes (8).Establishing a process for selecting, assessing, and advancing potential vaccine candidates is a critical issue for the melioidosis research community.Several vaccine candidates have been shown to provide partial protection in murine models of infection (8-10), but none have been tested to date in nonhuman primates (NHP) or humans.Possible candidates include live attenuated, whole-cell killed, subunit, glycoconjugate, outer membrane vesicle, plasmid DNA, and dendritic cell vaccines (8); possible candidates and candidate developments have been systematically reviewed and reported (8-10).A notable lack of standardization of protocols has resulted in variability in the animal models used (mice [BALB/c, C57BL/6, and Porton] and Syrian hamster); route of inoculation (intraperitoneal, intravenous, intranasal, intradermal, and subcutaneous); challenge strains (K96243, 1026b, 576, NCTC13392, NCTC4845, and NCTC13179); route of B. pseudomallei challenge (intraperitoneal, intravenous, aerosol inhalation, and intranasal); challenge dose; and duration of the followup period for assessing mortality rates among acute and chronic challenge models (5 days to 5 months) (8-10).As a result of the lack of consistency in use of specific methods on specific models, it is not possible to determine the comparative efficacy of different vaccine candidates.This inconsistency prevents researchers and officials in sponsoring and funding agencies from deciding which candidates should be advanced to NHP models.Recognizing these problems, our objectives were to assemble an expert group and arrive at consensus opinions and recommendations on candidate vaccines and animal models based on currently available evidence (8-10). Consensus on the Development of Vaccines against Naturally Acquired Melioidosis