Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
Virol J. 2018 Jan 19;15(1):17. doi: 10.1186/s12985-017-0918-y.
Influenza virus infection is an ongoing health and economic burden causing epidemics with pandemic potential, affecting 5-30% of the global population annually, and is responsible for millions of hospitalizations and thousands of deaths each year. Annual influenza vaccination is the primary prophylactic countermeasure aimed at limiting influenza burden. However, the effectiveness of current influenza vaccines are limited because they only confer protective immunity when there is antigenic similarity between the selected vaccine strains and circulating influenza isolates. The major targets of the antibody response against influenza virus are the surface glycoprotein antigens hemagglutinin (HA) and neuraminidase (NA). Hypervariability of the amino acid sequences encoding HA and NA is largely responsible for epidemic and pandemic influenza outbreaks, and are the consequence of antigenic drift or shift, respectively. For this reason, if an antigenic mismatch exists between the current vaccine and circulating influenza isolates, vaccinated people may not be afforded complete protection. There is currently an unmet need to develop an effective "broadly-reactive" or "universal" influenza vaccine capable of conferring protection against both seasonal and newly emerging pre-pandemic strains. A number of novel influenza vaccine approaches are currently under evaluation. One approach is the elicitation of an immune response against the "Achille's heel" of the virus, i.e. conserved viral proteins or protein regions shared amongst seasonal and pre-pandemic strains. Alternatively, other approaches aim toward eliciting a broader immune response capable of conferring protection against the diversity of currently circulating seasonal influenza strains.In this review, the most promising under-development universal vaccine approaches are discussed with an emphasis on those targeting the HA glycoprotein. In particular, their strengths and potential short-comings are discussed. Ultimately, the upcoming clinical evaluation of these universal vaccine approaches will be fundamental to determine their effectiveness against preventing influenza virus infection and/or reducing transmission and disease severity.
流感病毒感染是一种持续存在的健康和经济负担，具有流行潜力，每年影响全球 5-30%的人口，导致数百万人住院和数千人死亡。每年接种流感疫苗是限制流感负担的主要预防措施。然而，目前流感疫苗的效果有限，因为只有当选定的疫苗株与流行的流感分离株之间存在抗原相似性时，它们才能提供保护性免疫。针对流感病毒的抗体反应的主要靶标是表面糖蛋白抗原血凝素 (HA) 和神经氨酸酶 (NA)。编码 HA 和 NA 的氨基酸序列的高度变异性在很大程度上导致了流感的爆发和大流行，分别是抗原漂移或转变的结果。因此，如果当前疫苗与流行的流感分离株之间存在抗原不匹配，接种疫苗的人可能无法获得完全的保护。目前需要开发一种有效的“广泛反应性”或“通用”流感疫苗，能够提供针对季节性和新出现的大流行前流感株的保护。目前正在评估许多新的流感疫苗方法。一种方法是针对病毒的“阿喀琉斯之踵”，即季节性和大流行前株之间共享的保守病毒蛋白或蛋白区域，引发免疫反应。或者，其他方法旨在引发更广泛的免疫反应，能够提供针对当前流行的季节性流感株多样性的保护。在这篇综述中，讨论了最有前途的正在开发的通用疫苗方法，重点是针对 HA 糖蛋白的方法。特别是，讨论了它们的优缺点。最终，这些通用疫苗方法的临床评估将是确定它们在预防流感病毒感染和/或降低传播和疾病严重程度方面的有效性的关键。
