Clinical and vaccine immunology : CVI
-
Clin. Vaccine Immunol. · Jun 2009
Evaluation of a novel therapeutic approach to treating severe pneumococcal infection using a mouse model.
P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a previous study, we successfully recreated this phenomenon in mice in vivo by using a two-dose regimen of P4 and pathogen-specific antibodies, which significantly reduced moribundity in mice. For the present study, we hypothesized that the inclusion of a low-dose antibiotic would make it possible to treat the infected mice with a single dose containing a mixture of P4 and a pathogen-specific antibody. ⋯ Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by >80% over the control level; P < 0.05). This finding supports our hypothesis that PMN are activated by P4 during opsonophagocytosis and the recovery of mice from pneumococcal infection. P4 peptide-based combination therapy may offer an alternative and rapid immunotherapy to treat fulminant pneumococcal infection.
-
Clin. Vaccine Immunol. · May 2009
Comparative StudyTwo-step Epstein-Barr virus immunoglobulin A enzyme-linked immunosorbent assay system for serological screening and confirmation of nasopharyngeal carcinoma.
Undifferentiated nasopharyngeal carcinoma (NPC; WHO type III) is 100% associated with Epstein-Barr virus (EBV) infection and the fourth most prevalent cancer in Indonesian males. Therapy failure is high, since most patients come to the hospital at an advanced stage of disease. Screening for early-stage NPC is needed. ⋯ Results showed that 5/11 discrepant NPC samples with an elevated IgA EA ELISA also had elevated an EBV DNA load in the circulation (range, 3,200 to 25,820 copies/ml). Therefore, the IgA EA ELISA is proposed as a confirmation test in first-line NPC serological screening studies. This two-step EBV ELISA system provides a standardized approach for NPC screening and may be used in combination with dried blood sampling in future field studies for identification of early-stage NPC in high-risk regions.
-
Clin. Vaccine Immunol. · Jan 2009
Humoral and cellular immune responses induced by 3a DNA vaccines against severe acute respiratory syndrome (SARS) or SARS-like coronavirus in mice.
Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. ⋯ The vaccines stimulated gamma interferon production mainly by CD8(+) T cells and interleukin-2 (IL-2) mainly by CD4(+) T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.
-
Clin. Vaccine Immunol. · Dec 2008
Downregulation of CD40 ligand response in monocytes from sepsis patients.
It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. ⋯ In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.
-
Clin. Vaccine Immunol. · Nov 2008
Orally administered Mycobacterium vaccae modulates expression of immunoregulatory molecules in BALB/c mice with pulmonary tuberculosis.
The environmental saprophyte Mycobacterium vaccae induces a Th1 response and cytotoxic T cells that recognize M. tuberculosis, and by subcutaneous injection, it is therapeutic for pulmonary tuberculosis (TB) induced by high-dose challenge in BALB/c mice. However, M. vaccae also drives regulatory T cells that inhibit Th2 responses, and this is seen in allergy models, not only following subcutaneous injection but also after oral administration. An oral immunotherapeutic for TB would be clinically useful, so we investigated M. vaccae given orally by gavage at 28-day intervals in the TB model. ⋯ When administered 1 day before infection, oral M. vaccae induced a striking peak of expression of hemoxygenase 1. In conclusion, we show novel information about the expression in TB of murine IL-4delta2 and molecules involved in immunoregulation and show that these can be modulated by oral administration of a saprophytic mycobacterium. A clinical trial of oral M. vaccae in extensively drug-resistant TB might be justified.