Vogel Frederick R, Caillet Catherine, Kusters Inca C, Haensler Jean
Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France.
Expert Rev Vaccines. 2009 Apr;8(4):483-92. doi: 10.1586/erv.09.5.
The ongoing epizootic of highly pathogenic avian H5N1 influenza and its direct transmissibility and high pathogenicity in humans has led to renewed interest in the development of influenza vaccines with enhanced immunogenicity. Influenza vaccines are currently under development against influenza strains that are potentially pandemic threats, such as H5N1, as well as against the current seasonal influenza strains for use in populations susceptible to severe influenza disease. Influenza vaccines may be generally divided into two types: seasonal vaccines for use in a population that is largely primed to subtypes of the circulating influenza A strains and pandemic influenza vaccines that are designed to protect against influenza A viruses of a hemagglutinin (HA) subtype, to which the vast majority of the population is immunologically naive. Pandemic influenza vaccines can be further subdivided into prepandemic vaccines produced for use prior to or just after the declaration of a pandemic, and pandemic influenza vaccines that would be produced and used only after a pandemic is declared. Prepandemic influenza vaccines are formulated using HA and neuraminidase, which are likely to be antigenically similar to the influenza virus subtype deemed to pose the most probable pandemic threat. Enhanced vaccine immunogenicity is desirable for pandemic influenza vaccines and for seasonal vaccines used in target populations, such as the elderly, in which vaccine responses against the circulating influenza subtypes may be weak. Various methods to enhance the immunogenicity of influenza vaccines are under evaluation. Along with dose escalation and alternative delivery routes, strategies for improving the immunogenicity of influenza vaccines have focused on the use of immunologic adjuvants. An adjuvanted seasonal influenza vaccine, Fluad, has been licensed in some countries in Europe since 1997 for the elderly population, and a number of clinical trials have been completed or are in progress evaluating the use of adjuvants with pandemic and seasonal influenza vaccines. This review will focus on the use of emulsion-based adjuvants for enhancing the immunogenicity of pandemic influenza vaccines and of seasonal influenza vaccines in target populations.
高致病性禽流感H5N1的持续流行及其在人类中的直接传播性和高致病性，引发了人们对开发具有更强免疫原性的流感疫苗的新兴趣。目前正在研发针对具有潜在大流行威胁的流感毒株（如H5N1）的流感疫苗，以及针对当前季节性流感毒株、供易患严重流感疾病人群使用的疫苗。流感疫苗通常可分为两类：一类是用于对正在流行的甲型流感毒株亚型已有一定免疫基础人群的季节性疫苗，另一类是旨在预防绝大多数人群在免疫上尚未接触过的血凝素（HA）亚型甲型流感病毒的大流行性流感疫苗。大流行性流感疫苗可进一步细分为在大流行宣布之前或之后不久生产使用的大流行前疫苗，以及仅在大流行宣布后才生产和使用的大流行性流感疫苗。大流行前流感疫苗是使用HA和神经氨酸酶配制的，这些成分在抗原性上可能与被认为构成最可能大流行威胁的流感病毒亚型相似。对于大流行性流感疫苗以及用于目标人群（如老年人）的季节性疫苗而言，增强疫苗免疫原性是很有必要的，因为这些人群针对正在流行的流感亚型的疫苗反应可能较弱。目前正在评估各种增强流感疫苗免疫原性的方法。除了增加剂量和采用替代给药途径外，提高流感疫苗免疫原性的策略主要集中在使用免疫佐剂方面。一种含有佐剂的季节性流感疫苗Fluad自1997年起已在欧洲一些国家获得许可，用于老年人群，并且已经完成或正在进行多项临床试验，评估佐剂在大流行性流感疫苗和季节性流感疫苗中的应用。本综述将重点关注基于乳剂的佐剂在增强大流行性流感疫苗和目标人群季节性流感疫苗免疫原性方面的应用。
