United States: No licensed antidote exists for safeguarding against melioidosis, an equatorial ailment that claims approximately 89,000 lives annually. Scholars aspire to revolutionize this circumstance through the introduction of a fresh antidote contender they’ve formulated targeting B. pseudomallei, the microbe accountable for the ailment.
The recent antidote employs an adapted form of a microorganism to securely convey the molecules that trigger an immunological reaction within the host’s cells. This “carrier” is identical to the one utilized in the creation of successful antidotes against anthrax, the Black Death, and tularemia, also recognized as rabbit fever, according to Advanced Science News.
“The carrier itself, dubbed LVS delta capB is derived from an antidote against tularemia referred to as live vaccine strain or LVS,” stated Marcus Horwitz, doctor of medicine and expert in microbiology, immunology, and molecular genetics at the UCLA School of Medicine and primary author of the exploration.
Tularemia is a potentially lethal ailment that typically afflicts rabbits, hares, and rodents but can also extend to humans. The original live vaccine strain contains an attenuated form of a microorganism that induces tularemia.
Although it confers some protection against infection, the antidote also poses toxicity risks and may prompt lymph node inflammation and discomfort at the injection site in up to 80% of recipients, as mentioned by Advanced Science News.
To tackle the toxicity dilemma, researchers eliminated a gene named capB, resulting in over 10,000 times reduced toxicity compared to the original antidote. Subsequently, to forge the melioidosis antidote, they integrated four distinct B. pseudomallei genes encoding the blueprints for synthesizing proteins known to provoke an immunological response.
Defenses against the deadliest manifestation of melioidosis
Humans can contract melioidosis through various means: by ingesting water or food contaminated with B. pseudomallei, by direct contact with the microbe through a skin injury, or by inhaling contaminated airborne particles. “Infection via the respiratory pathway with B. pseudomallei is deemed the most lethal and challenging route to safeguard against,” asserted Horwitz.
To evaluate the efficacy of their antidote against this infection route, researchers selected mice exhibiting 10 to 100 times heightened sensitivity to B. pseudomallei compared to other research strains and immunized them by delivering a small dose of the fresh antidote into each nasal passage. The mice received three doses of the antidote, spaced four weeks apart. Subsequently, four weeks after the final dose, they were exposed to a lethal dose of B. pseudomallei, also administered nasally.
The researchers juxtaposed their findings with those of a control group subjected to a “sham” immunization, but they also compared them to mice immunized with the fresh antidote via subcutaneous injection. Finally, to gauge the effectiveness of their antidote against an existing one, they compared the outcomes to a control group inoculated with a melioidosis antidote deemed efficacious but unsuitable for human use.
Administering the antidote via the nasal route proved more efficacious than conventional injection, even against high B. pseudomallei doses. Mice receiving the fresh antidote nasally exhibited a median survival rate of 75% at 42 days; a separate trial verified that even a sole dose of the intranasal antidote conferred comparable protection. When delivered nasally, the fresh antidote matched or surpassed the effectiveness of the control antidote, Advanced Science News mentioned.
Potential global significance
Melioidosis infects thousands of individuals naturally, yet it is also classified as a Tier 1 Select Agent, signifying health authorities perceive it as having substantial potential for biological weapon employment.
“The availability of a safe and efficacious antidote [against melioidosis] holds significance for global health security,” remarked Wesley Long, director of medical microbiology diagnostics at Houston Methodist Hospital, unaffiliated with the study.
Long added that additional investigations are imperative before determining the antidote’s efficacy in humans. “At present, all research has been conducted in mice,” he remarked. “Before transitioning to humans, initial clinical trials for safety, followed by efficacy assessments, must be undertaken, with results potentially differing from those observed in murine models.”
Before human trials commence, Horwitz mentioned the necessity to assess the antidote’s efficacy in a secondary animal model. “The Food and Drug Administration (FDA) mandates this for vaccines where efficacy studies are otherwise unattainable,” he explained. “Should the antidote perform well in a secondary animal model, it would become eligible for human safety and immunogenicity trials,” as outlined by Advanced Science Study.
Additionally, Horwitz expressed the desire to investigate whether the antidote can safeguard against infections stemming from contact with B. pseudomallei through skin abrasions. They also intend to assess its efficacy against a related microbe known as B. mallei.
“This pathogen triggers glanders in humans and animals and is similarly categorized as a Tier 1 Select Agent for bioterrorism,” Horwitz elaborated. “B. mallei shares certain antigens expressed by our antidote.” Should the antidote exhibit promise in these investigations, it could emerge as a pivotal defense against not one but two significant diseases, potentially preserving myriad lives.