• Report on eighth WHO meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses: Chicago, USA, 23–24 August 2016

      Ortiz, Justin R.; Hickling, Julian; Neuzil, Kathleen M. (Elsevier Ltd., 2018-02-08)
      In August 2016, the World Health Organization (WHO) convened the “Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses” to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines, and to identify areas where WHO can promote the development of such vaccines. Participants included approximately 120 representatives of academia, the vaccine industry, research and development funders, and regulatory and public health agencies. They reviewed the draft WHO preferred product characteristics (PPCs) of vaccines that could address prioritized unmet public health needs and discussed the challenges facing the development of such vaccines, especially for low- and middle-income countries (LMIC). They defined the data desired by public-health decision makers globally and explored how to support the progression of promising candidates into late-stage clinical trials and for all countries. This report highlights the major discussions of the meeting. © 2017 World Health Organization.
    • Salmonella Typhi Colonization Provokes Extensive Transcriptional Changes Aimed at Evading Host Mucosal Immune Defense During Early Infection of Human Intestinal Tissue

      Nickerson, K. P.; Senger, S.; Fraser, Claire M. (Elsevier B.V., 2018-05-01)
      Commensal microorganisms influence a variety of host functions in the gut, including immune response, glucose homeostasis, metabolic pathways and oxidative stress, among others. This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples and “mini-guts,” organoids grown from intestinal tissue taken from biopsy specimens. We analyzed gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection. This work adds novel information regarding S. Typhi infection pathogenesis in humans, by replicating work shown in traditional cell models, and providing new data that can be applied to future vaccine development strategies. © 2018 The Authors