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Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine.
Infect Immun. 2013 Dec; 81(12):4626-34.II

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, vaccine-induced 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.

Authors+Show Affiliations

Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research and Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24101688

Citation

Silva, Ediane B., et al. "Correlates of Immune Protection Following Cutaneous Immunization With an Attenuated Burkholderia Pseudomallei Vaccine." Infection and Immunity, vol. 81, no. 12, 2013, pp. 4626-34.
Silva EB, Goodyear A, Sutherland MD, et al. Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine. Infect Immun. 2013;81(12):4626-34.
Silva, E. B., Goodyear, A., Sutherland, M. D., Podnecky, N. L., Gonzalez-Juarrero, M., Schweizer, H. P., & Dow, S. W. (2013). Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine. Infection and Immunity, 81(12), 4626-34. https://doi.org/10.1128/IAI.00915-13
Silva EB, et al. Correlates of Immune Protection Following Cutaneous Immunization With an Attenuated Burkholderia Pseudomallei Vaccine. Infect Immun. 2013;81(12):4626-34. PubMed PMID: 24101688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine. AU - Silva,Ediane B, AU - Goodyear,Andrew, AU - Sutherland,Marjorie D, AU - Podnecky,Nicole L, AU - Gonzalez-Juarrero,Mercedes, AU - Schweizer,Herbert P, AU - Dow,Steven W, Y1 - 2013/10/07/ PY - 2013/10/9/entrez PY - 2013/10/9/pubmed PY - 2014/1/9/medline SP - 4626 EP - 34 JF - Infection and immunity JO - Infect Immun VL - 81 IS - 12 N2 - 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, vaccine-induced 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. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/24101688/Correlates_of_immune_protection_following_cutaneous_immunization_with_an_attenuated_Burkholderia_pseudomallei_vaccine_ L2 - https://journals.asm.org/doi/10.1128/IAI.00915-13?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -