Combining Monophosphoryl Lipid A (MPL), CpG Oligodeoxynucleotide (ODN), and QS-21 Adjuvants Induces Strong and Persistent Functional Antibodies and T Cell Responses against Cell-Traversal Protein for Ookinetes and Sporozoites (CelTOS) of Plasmodium falciparum in BALB/c Mice
INFECTION AND IMMUNITY
Authors: Pirahmadi, Sakineh; Zakeri, Sedigheh; Mehrizi, Akram A.; Djadid, Navid D.; Raz, Abbas-Ali; Sani, Jafar J.
Abstract
Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an advanced vaccine candidate that has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts. As recombinant purified proteins are normally poor immunogens, they require to be admixed with an adjuvant(s); therefore, the objective of the present study was to evaluate the capacity of different vaccine adjuvants, monophosphoryl lipid A (MPL), CpG, and Quillaja saponaria Molina fraction 21 (QS-21), alone or in combination (MCQ [MPL/CpG/QS-21]), to enhance the immunogenicity of Escherichia coli-expressed PfCelTOS in BALB/c mice. This goal was achieved by the assessment of anti-PfCelTOS IgG anti-bodies (level, titer, IgG isotype profile, avidity, and persistence) and extracellular Th1 cytokines using an enzyme-linked immunosorbent assay (ELISA) on postimmunized BALB/c mouse sera and PfCelTOS-stimulated splenocytes, respectively. Also, an assessment of the transmission-reducing activity (TRA) of anti-PfCelTOS obtained from different vaccine groups was carried out in female Anopheles stephensi mosquitoes by using a standard membrane feeding assay (SMFA). In comparison to PfCelTOS alone, administration of PfCelTOS with three distinct potent Th1 adjuvants in vaccine mouse groups showed enhancement and improvement of PfCelTOS immunogenicity that generated more bias toward a Th1 response with significantly enhanced titers and avidity of the anti-PfCelTOS responses that could impair ookinete development in A. stephensi. However, immunization of mice with PfCelTOS with MCQ mixture adjuvants resulted in the highest levels of induction of antibody titers, avidity, and inhibitory antibodies in oocyst development (88%/26.7% reductions in intensity/prevalence) in A. stephensi. It could be suggested that adjuvant combinations with different mechanisms stimulate better functional antibody responses than adjuvants individually against challenging diseases such as malaria.
Should laparoscopic lymph node biopsy be the preferred diagnostic modality for isolated abdominal lymphadenopathy?
CURRENT ONCOLOGY
Authors: Gilbert, R. W. D.; Bird, B. H.; Murphy, M. G.; O'Boyle, C. J.
Abstract
Background Isolated abdominal lymphadenopathy is frequently detected, but often challenging to diagnose. To obtain a tissue diagnosis, percutaneous biopsy (PB) or laparoscopic biopsy (LB) is often undertaken. The safety profiles and diagnostic accuracy of PB and LB within the abdomen are both poorly defined. Methods In this retrospective analysis, we identified all patients who underwent LB or PB for isolated abdominal lymphadenopathy at our institute during 2008-2016. Results Of 62 patients who underwent nodal biopsy for isolated abdominal lymphadenopathy, 33 underwent LB and 29 underwent PB. For the 33 patients who underwent LB, the procedure was diagnostic in 100% of cases; for the 29 who underwent PB, the procedure was diagnostic in 18 cases (62.1%). Both procedures were safe, with similar complication rates (6.0% for LB; 7.0% for PB). Conclusions Our results establish that LB and PB are both safe and reliable in the setting of isolated abdominal lymphadenopathy. We also demonstrate that each procedure has situational advantages. A PB should be considered to be the upfront diagnostic modality, particularly when anatomic or disease factors favour its success. In situations in which it is felt that PB cannot safely access the lymphadenopathy or in disease states in which the yield of a core biopsy will be insufficient, us should be strongly considered. Examples include ex tra-ret roperitoneal lymphadenopathy and cases of suspected lymphoma.