Transmission Of Vaccine Strain Research Articles

An Ad/MVA vectored Theileria parva antigen induces schizont-specific CD8+ central memory T cells and confers partial protection against a lethal challenge

The parasite Theileria parva is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers’ livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a cold chain, and antibiotics limit its utilization. This has fostered research towards subunit vaccination. Cytotoxic T lymphocytes (CTL) are crucial in combating the infection by lysing T. parva-infected cells. Tp1 is an immunodominant CTL antigen, which induces Tp1-specific responses in 70–80% of cattle of the A18 or A18v haplotype during vaccination with the live vaccine. In this study, human adenovirus serotype 5 (HAd5) and modified vaccinia Ankara (MVA) were assessed for their ability to induce Tp1-specific immunity. Both viral vectors expressing the Tp1 antigen were inoculated in cattle by a heterologous prime-boost vaccination regimen. All 15 animals responded to Tp1 as determined by ELISpot. Of these, 14 reacted to the known Tp1 epitope, assayed by ELISpot and tetramer analyses, with CTL peaking 1-week post-MVA boost. Eleven animals developed CTL with specific cytotoxic activity towards peripheral blood mononuclear cells (PBMC) pulsed with the Tp1 epitope. Moreover, 36% of the animals with a Tp1 epitope-specific response survived a lethal challenge with T. parva 5 weeks post-MVA boost. Reduction of the parasitemia correlated with increased percentages of central memory lymphocytes in the Tp1 epitope-specific CD8+ populations. These results indicate that Tp1 is a promising antigen to include in a subunit vaccine and central memory cells are crucial for clearing the parasite.

Chronic Steroid and Immunosuppressant Therapy in Children

1. Abraham Gedalia, MD* 2. Avinash K. Shetty, MD† 1. *Professor of Pediatrics and Head, Division of Pediatric Rheumatology, Louisiana State University Health Sciences Center and Children’s Hospital, New Orleans, La 2. †Assistant Professor of Pediatrics, Division of Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC After completing this article, readers should be able to: 1. Describe the mechanism of action, list indications for therapy, and discuss the adverse effects of corticosteroid therapy in children. 2. Delineate the mechanism of action and adverse effects of other immunosuppressive agents frequently used in children. 3. Discuss the immunization recommendations for children receiving immunosuppressive therapy. Corticosteroids are the most potent, naturally occurring anti-inflammatory agents known. Despite more than 50 years of controversy regarding their clinical use, risks, and benefits, corticosteroids still play a significant role in the management of a wide variety of diseases. They have reduced the morbidity and mortality significantly in children afflicted with leukemia, asthma, rheumatic diseases, and other inflammatory disorders. In this article, we review the mechanism of action, clinical indications, and adverse effects of corticosteroids and other commonly used immunosuppressive agents in children. We also review immunization recommendations for children receiving immunosuppressive therapy. Corticosteroids have a diverse role in the human body at the physiologic level. The actions of glucocorticoids include: 1) negative feedback modulation of corticotropin-releasing factor and adrenocorticotropic hormone; 2) regulation of blood glucose and liver glycogen levels; 3) maintenance of water-electrolyte homeostasis; 4) influence on the metabolism of protein, fat, and purine; 5) maintenance of normal cardiovascular, central nervous system (CNS), and renal functions; 6) influence on circadian rhythmicity; 7) maintenance of bone and muscle work capacity; and 8) protection of the body against moderate stress. Glucocorticoids also have pharmacologic properties that are used in the treatment of rheumatic and other inflammatory diseases. Cellular receptors for cortisol are ubiquitous in cell cytoplasm, reflecting the critical role of the hormone in maintaining cell homeostasis. The type 1 glucocorticoid receptor, known as the mineralocorticoid receptor, has high affinity for aldosterone. The type 2 glucocorticoid receptor, known as the glucocorticoid receptor, exhibits strong affinity for dexamethasone. Although …