Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

Abstract

Infections with the Gram-negative bacterium Burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with B. pseudomallei. At present, our understanding of what constitutes effective protective immunity against B. pseudomallei infection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acute B. pseudomallei infection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excluded purM deletion mutant of B. pseudomallei (strain Bp82) and then subjected to intranasal challenge with virulent B. pseudomallei strain 1026b. Immunization with Bp82 generated significant protection from challenge with B. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccineinduced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuated Burkholderia vaccine strain was dependent primarily on generation of effective humoral immune responses.

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

“…7A). These findings are consistent with previous reports indicating that high Th1 bias antibody titers afford superior protection (109,(130)(131)(132)(133). Our data also underscore a protective role for antibodies of the IgG subclass ( Fig.…”

Burkholderia pseudomallei Capsular Polysaccharide Conjugates Provide Protection against Acute Melioidosis

“…It is interesting that CPS2B1, which would be predicted to stimulate protective anti-CPS humoral responses only (since cBSA is not a B. pseudomallei protein), resulted in greater survival than did B. pseudomallei LolC, which has the potential to elicit both protective humoral and cell-mediated responses. This finding supports recent findings by Silva et al that suggest that humoral immunity is critically important for vaccineinduced protection against acute disease (44).…”

A Burkholderia pseudomallei Outer Membrane Vesicle Vaccine Provides Protection against Lethal Sepsis

“…These results attest to the protective efficacy of the antibody response induced by immunization with B. pseudomallei-derived OMVs. Our results are in agreement with recent work showing that the protection afforded by immunization with a live B. pseudomallei ⌬purM (Bp82) vaccine is dependent primarily on humoral immunity (41). It will be informative to determine the relative contributions of OMV proteins and polysaccharides to OMV vaccine-mediated protection and to evaluate the breadth of cross-protection against additional B. pseudomallei strains in future studies.…”