Sealy Robert E, Jones Bart G, Surman Sherri L, Penkert Rhiannon R, Pelletier Stephane, Neale Geoff, Hurwitz Julia L
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vaccines (Basel). 2019 Feb 27;7(1):26. doi: 10.3390/vaccines7010026.
Despite extraordinary advances in fields of immunology and infectious diseases, vaccine development remains a challenge. The development of a respiratory syncytial virus vaccine, for example, has spanned more than 50 years of research with studies of more than 100 vaccine candidates. Dozens of attractive vaccine products have entered clinical trials, but none have completed the path to licensing. Human immunodeficiency virus vaccine development has proven equally difficult, as there is no licensed product after more than 30 years of pre-clinical and clinical research. Here, we examine vaccine development with attention to the host. We discuss how nuclear hormones, including vitamins and sex hormones, can influence responses to vaccines. We show how nuclear hormones interact with regulatory elements of immunoglobulin gene loci and how the deletion of estrogen response elements from gene enhancers will alter patterns of antibody isotype expression. Based on these findings, and findings that nuclear hormone levels are often insufficient or deficient among individuals in both developed and developing countries, we suggest that failed vaccine studies may in some cases reflect weaknesses of the host rather than the product. We encourage analyses of nuclear hormone levels and immunocompetence among study participants in clinical trials to ensure the success of future vaccine programs.
尽管免疫学和传染病领域取得了非凡进展，但疫苗研发仍然是一项挑战。例如，呼吸道合胞病毒疫苗的研发历经了50多年的研究，涉及100多种候选疫苗。数十种有吸引力的疫苗产品已进入临床试验，但无一完成获批流程。事实证明，人类免疫缺陷病毒疫苗的研发同样困难，经过30多年的临床前和临床研究，仍没有获批产品。在此，我们从宿主的角度审视疫苗研发。我们讨论包括维生素和性激素在内的核激素如何影响对疫苗的反应。我们展示了核激素如何与免疫球蛋白基因位点的调控元件相互作用，以及从基因增强子中删除雌激素反应元件将如何改变抗体亚型表达模式。基于这些发现，以及发达国家和发展中国家个体中核激素水平往往不足或缺乏的发现，我们认为疫苗研究失败在某些情况下可能反映了宿主的弱点而非产品问题。我们鼓励在临床试验中分析研究参与者的核激素水平和免疫能力，以确保未来疫苗项目的成功。
