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Published on: February 24, 2023
Progress toward development of vaccines against melioidosis: A review
Mitali Sarkar-Tyson1, Richard W Titball
1Defence Science and Technology Laboratory, Salisbury, United Kingdom. MSTYSON@mail.dstl.gov.uk
Background:
Melioidosis is a serious and often fatal disease that is prevalent in subtropical and tropical climates, primarily in at-risk groups (eg, those with diabetes, alcoholism, or other cause of immunosuppression). Treatment is often unsuccessful, with infection frequently relapsing. Burkholderia pseudomallei, the etiologic agent of melioidosis, is inherently resistant to many antibiotics.
Objective:
This article reviews available evidence on the development of vaccines against melioidosis, including live attenuated vaccines, inactivated whole cell vaccines, and recombinant subunit vaccines.
Methods:
Web of Science and PubMed (1950-February 2010) were searched for relevant reports using the term Burkholderia pseudomallei alone and combined with live attenuated vaccine, inactivated vaccine, animal models, and immunity. The reference lists of identified articles were reviewed for additional relevant publications.
Results:
Studies in murine models suggest that protective immunity against B pseudomallei may be induced by a range of living and nonliving immunogens. The strongest protective immunity was induced by live attenuated immunogens, although concerns about latency make it unlikely that such vaccines will be appropriate for use in humans. Heat-inactivated immunogens have shown promise, and several candidates for subunit vaccines have been tested. However, in all cases, it has been difficult to achieve induction of sterile immunity and protection against airborne infection.
Conclusions:
Live attenuated mutants of B pseudomallei have been found to be the most effective immunogens in mice, although it is unlikely that such mutants would be appropriate for a vaccine against melioidosis in humans. The ongoing challenge is to identify nonliving formulations that are able to induce good protective immunity. Both humoral and cell-mediated immunity are likely to be required. In this respect, naked DNA vaccines have the potential to provide high-level protection.
Insights
Developing effective vaccines against melioidosis remains challenging. While live attenuated vaccines show promise in animal models, nonliving formulations inducing both humoral and cell-mediated immunity are needed for human use.
Area of Science:
- Infectious Diseases
- Vaccinology
- Microbiology
Background:
- Melioidosis is a severe, often fatal disease caused by Burkholderia pseudomallei, prevalent in tropical/subtropical regions.
- High-risk populations include individuals with diabetes, alcoholism, or immunosuppression.
- Current treatments are often unsuccessful due to antibiotic resistance and frequent relapses.
Purpose of the Study:
- To review existing evidence on vaccine development for melioidosis.
- To evaluate different vaccine types, including live attenuated, inactivated whole cell, and recombinant subunit vaccines.
Main Methods:
- Comprehensive literature search of Web of Science and PubMed (1950-February 2010).
- Keywords included Burkholderia pseudomallei, live attenuated vaccine, inactivated vaccine, animal models, and immunity.
- Reference lists of identified articles were cross-referenced for additional studies.
Main Results:
- Live attenuated immunogens induced the strongest protective immunity in murine models.
- Concerns regarding latency limit the human applicability of live attenuated vaccines.
- Heat-inactivated and subunit vaccines show promise but struggle to induce sterile immunity and protection against airborne infection.
Conclusions:
- Live attenuated B. pseudomallei mutants are effective in mice but not suitable for human melioidosis vaccines.
- Identifying nonliving vaccine formulations that induce robust protective immunity is crucial.
- Future vaccines may require both humoral and cell-mediated immune responses, with naked DNA vaccines showing potential.
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