O'Hagan Derek T, van der Most Robbert, Lodaya Rushit N, Coccia Margherita, Lofano Giuseppe
GSK, Rockville, MD, USA.
GSK, Rixensart, Belgium.
NPJ Vaccines. 2021 Dec 21;6(1):158. doi: 10.1038/s41541-021-00418-0.
Emulsion adjuvants such as MF59 and AS03 have been used for more than two decades as key components of licensed vaccines, with over 100 million doses administered to diverse populations in more than 30 countries. Substantial clinical experience of effectiveness and a well-established safety profile, along with the ease of manufacturing have established emulsion adjuvants as one of the leading platforms for the development of pandemic vaccines. Emulsion adjuvants allow for antigen dose sparing, more rapid immune responses, and enhanced quality and quantity of adaptive immune responses. The mechanisms of enhancement of immune responses are well defined and typically characterized by the creation of an "immunocompetent environment" at the site of injection, followed by the induction of strong and long-lasting germinal center responses in the draining lymph nodes. As a result, emulsion adjuvants induce distinct immunological responses, with a mixed Th1/Th2 T cell response, long-lived plasma cells, an expanded repertoire of memory B cells, and high titers of cross-neutralizing polyfunctional antibodies against viral variants. Because of these various properties, emulsion adjuvants were included in pandemic influenza vaccines deployed during the 2009 H1N1 influenza pandemic, are still included in seasonal influenza vaccines, and are currently at the forefront of the development of vaccines against emerging SARS-CoV-2 pandemic variants. Here, we comprehensively review emulsion adjuvants, discuss their mechanism of action, and highlight their profile as a benchmark for the development of additional vaccine adjuvants and as a valuable tool to allow further investigations of the general principles of human immunity.
诸如MF59和AS03之类的乳化佐剂作为已获许可疫苗的关键成分已使用了二十多年，在30多个国家向不同人群接种了超过1亿剂。大量的有效性临床经验、成熟的安全性概况以及易于生产，使乳化佐剂成为大流行疫苗开发的主要平台之一。乳化佐剂可减少抗原剂量、加快免疫反应，并提高适应性免疫反应的质量和数量。免疫反应增强的机制已得到充分明确，其典型特征是在注射部位形成“免疫活性环境”，随后在引流淋巴结中诱导强烈且持久的生发中心反应。因此，乳化佐剂可诱导独特的免疫反应，包括混合的Th1/Th2 T细胞反应、长寿浆细胞、记忆B细胞库扩大以及针对病毒变体的高滴度交叉中和多功能抗体。由于这些特性，乳化佐剂被纳入2009年甲型H1N1流感大流行期间部署的大流行性流感疫苗中，目前仍被纳入季节性流感疫苗中，并且在针对新出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行变体的疫苗开发中处于前沿地位。在此，我们全面综述乳化佐剂，讨论其作用机制，并强调其作为开发其他疫苗佐剂的基准以及作为进一步研究人类免疫一般原则的宝贵工具的概况。
