SM Vaccines and Vaccination Journal

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Development of a Whole-Cell Cancer Vaccine Containing Accumulated Intracellular Interleukin-15: Current Knowledge and Progression

Interest has focused on using potent immunostimulatory cytokines, such as IL-15, as an adjuvant for cancer treatment or as part of a vaccine therapy. This review presents an IFN-α-induced, whole-cell cancer vaccine in mice, contrasts this cancer vaccine with those reported in other studies, and considers its potential use as a human cancer vaccine. Initial studies focused on developing a B16 melanoma vaccine. B16 cells treated for ≥2 weeks with IFN-α become B16α vaccine cells that contain accumulated intracellular IL-15. Intraperitoneal, subcutaneous, and intravenous inoculations of irradiated B16α cells into mice have established adaptive immunity to B16 melanoma and the survival of a substantial fraction of the mice (60% survival with 4 vaccinations and >80% survival with 6 vaccinations). The immunity is specific to B16 melanoma; is active systemically against metastases; demonstrates memory; and, is dependent on the function of macrophages, NK cells, CD4+ helper T cells, and CD8+ cytotoxic T cells, by using corresponding knock-out mice. Thus, B16α cells are “bags” of IL-15 that express melanoma surface antigens. After inoculating irradiated B16α cells into mice, melanomaspecific tissue-infiltrating lymphocytes gather at the inoculation site. When the irradiated B16α cells lyse, they release their accumulated IL-15 as a bolus, activating the melanoma-specific tissue-infiltrating lymphocytes. The activated lymphocytes proliferate and kill B16 melanoma cells throughout the body. While initial studies were focused on developing B16α cells as a melanoma vaccine, the IFN-α treatment protocol has been employed to develop RM-1α cells and P388α cells as vaccines against RM-1 prostate cancer and against P388 lymphocytic leukemia, respectively. The demonstration of efficacious vaccines against multiple cancers supports the general applicability of the IL-15-containing whole-cell vaccine. The relative efficacies of the different vaccines appear to be associated with a relative down-regulation of translation of the IL-15 mRNA. To achieve the full potential of the vaccines, it will be necessary to transfect cancer cells with constructs of IL-15 that negate the down-regulatory mechanisms. Since mouse and human immune systems illustrate many common features of IL-15 function, these studies have high promise of being extended to the creation of human cancer vaccines.

Daniel P Griffin1 and W Robert Fleischmann Jr1*


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Global Health Challenges: Failure of Measles Vaccination Coverage in Nigeria

Vaccine-preventable diseases are the most common cause of childhood mortality, with an estimated three million deaths each year [1]. Over 20 million children across the globe are unvaccinated against measles, tetanus, rubella or polio [2]. Half of these children come from ten countries, five of which are in Africa. Nigeria, Ethiopia, the Democratic Republic of Congo, Uganda, and South Africa have the largest numbers of unvaccinated or under-vaccinated children on the continent [2]. In an era of a well-developed and cost-effective vaccine against measles, it is imperative that we address the continually high death rates from measles. A case in point is Nigeria, one of the worst performing countries in reaching universal vaccination for all vaccine-preventable diseases. Universal vaccination is defined as having at least over 90% of children less than one year vaccinated. Nigeria is the most populous country in Africa with a population of 173 million people; about 30 million are children under the age of 5 year. Nigeria is also the wealthiest in Sub-Saharan Africa. Still, one particular question remains unanswered: why does Nigeria continue to report nearly 3.5 million unvaccinated babies against measles?

Stephanie K King1 , Olivia G Mendel2 and Juliet N Sekandi2*


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Seth J. Worley, MD, FHRS, FACC

Director, Interventional Implant Program MedStar Heart & Vascular Institute, Washington, DC, USA

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