Chlamydia muridarum T-cell antigens formulated with the adjuvant DDA/TDB induce immunity against infection that correlates with a high frequency of gamma interferon (IFN-gamma)/tumor necrosis factor alpha and IFN-gamma/interleukin-17 double-positive CD4+ T cells.

Abstract

Major impediments to developing a Chlamydia vaccine lie in identifying immunologically relevant T-cell antigens and delivery in a manner to stimulate protective immunity. Using an immunoproteomic approach, we previously identified three immunodominant Chlamydia T-cell antigens (PmpG-1, PmpE/F-2, and RplF). Because RplF has high homology to a human ortholog, it may not be suitable for human vaccine development. Therefore, in this study, we evaluated protection against Chlamydia infection in the genital tract in C57BL/6 mice immunized with Chlamydia-specific membrane proteins PmpG-1, PmpE/F-2, and major outer membrane protein (MOMP; as a reference) or a combination of them formulated with one of three adjuvants, CpG oligodeoxynucleotide (CpG-ODN), AbISCO-100 (AbISCO), or DDA/TDB (dimethyldioctadecylammonium bromide/D-(+)-trehalose 6,6'-dibehenate). The results show that immunization with the CpG-ODN formulation failed to provide protection against Chlamydia infection; the AbISCO formulation conferred moderate protection, and the DDA/TDB formulation showed the highest degree of protective efficacy. The combination of PmpG-1, PmpE/F-2, and MOMP proteins formulated with DDA/TDB exhibited the greatest degree of protection among all vaccine groups studied. Moreover, this vaccine combination also engendered significant protection in BALB/c mice, which have a different major histocompatibility complex (MHC) background. We measured cell-mediated immune cytokine responses in mice immunized with PmpG-1 mixed with each of the three adjuvants. The results demonstrate that mice immunized with the DDA/TDB formulation induced the strongest gamma interferon (IFN-gamma) and interleukin-17 (IL-17) responses, characterized by the highest frequency of IFN-gamma/tumor necrosis factor alpha (TNF-alpha) and IFN-gamma/IL-17 double-positive CD4(+) T cells. In conclusion, a Chlamydia vaccine based on the recombinant proteins PmpG-1, PmpE/F-2, and MOMP delivered in a DDA/TDB adjuvant conferred protection against infection that correlated with IFN-gamma/TNF-alpha and IFN-gamma/IL-17 double-positive CD4(+) T cells.

• Authors: Hong Yu, Xiaozhou Jiang, Caixia Shen, Karuna P Karunakaran, Janina Jiang, Nicole L Rosin, Robert C Brunham
• Journal: Infection and immunity (Infect Immun) Vol. 78 Issue 5 Pg. 2272-82 (May 2010) ISSN: 1098-5522 [Electronic] United States
• PMID: 20231405 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Antigens, Bacterial
• Bacterial Vaccines
• Interleukin-17
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, Bacterial (immunology)
• Bacterial Vaccines (immunology)
• CD4-Positive T-Lymphocytes (chemistry, immunology)
• Chlamydia Infections (immunology, prevention & control)
• Chlamydia muridarum (immunology)
• Female
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• T-Lymphocyte Subsets (immunology)
• Tumor Necrosis Factor-alpha (metabolism)