Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, VIC 3000, Australia.
Drug Delivery, Disposition and Dynamics Laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.
Vaccine. 2017 Nov 7;35(47):6451-6458. doi: 10.1016/j.vaccine.2017.09.062. Epub 2017 Oct 10.
Globally the most commonly utilised immunisation against influenza is the trivalent inactivated influenza vaccine (TIV) derived from an A/H1N1, an A/H3N2 and aB type influenza virus. Vaccine effectiveness of TIV varies year to year, depending on how well antigenically matched the strains in the vaccine are compared to circulating strains [1,2]. Moreover, vaccine effectiveness can vary within certain subpopulations such as HIV-positive, young children and the elderly. Decreased vaccine effectiveness in the elderly is associated with impaired Ab production, as measured by standard hemagglutination inhibition (HAI) assays. We investigated the level of Antibody Dependent Phagocytosis (ADP)-mediating Abs induced by the 2008-TIV in healthy Australian adults aged over and under 60years to determine if this immune function was also reduced in the elderly. We utilised an ADP assay that measures the uptake of IgG-opsonised HA-coated fluorescent microspheres by a monocytic cell line. We also measured HA-specific Abs that are close enough to bind to dimeric FcγRIIa ectodomains in an ELISA-based assay. Furthermore, we compared the extent of cross-reactive recognition of diverse influenza strains by ADP-mediating Abs found in pre- and post-vaccination sera in both of these groups. We found that young adults and older adults mounted similar ADP activity against HAs contained in the 2008-TIV, despite older adults have diminished HI responses. The level of cross-reactive antibodies against other HAs was limited in both groups. We conclude that seasonal influenza vaccination elicits limited cross-reactive ADP to HA in both young and older adults. New influenza vaccination strategies that elicit cross-reactive and polyfunctional antibodies are needed.
全球最常用的流感疫苗是三价灭活流感疫苗（TIV），由 A/H1N1、A/H3N2 和 B 型流感病毒衍生而来。TIV 的疫苗效力每年都有所不同，这取决于疫苗中的毒株与流行株的抗原匹配程度[1,2]。此外，疫苗效力在某些特定人群中可能会有所不同，如 HIV 阳性者、幼儿和老年人。老年人疫苗效力下降与 Ab 产生受损有关，这可以通过标准血凝抑制（HAI）测定来衡量。我们研究了 2008 年 TIV 在澳大利亚健康成年人中的抗体依赖性吞噬作用（ADP）介导的 Abs 水平，以确定这种免疫功能是否也会随着年龄的增长而降低。我们利用 ADP 测定法来测量 IgG 包被的 HA 涂层荧光微球被单核细胞系摄取的情况。我们还利用 ELISA 测定法测量了与二聚体 FcγRIIa 胞外结构域足够接近以结合的 HA 特异性 Abs。此外，我们比较了这两组人群中接种前后血清中 ADP 介导的 Abs 对多种流感株的交叉识别程度。我们发现，尽管老年人的 HAI 反应减弱，但年轻人和老年人对 2008 年 TIV 中包含的 HA 产生了相似的 ADP 活性。两组人群对其他 HA 的交叉反应性抗体水平都有限。我们得出的结论是，季节性流感疫苗接种会在年轻人和老年人中引发针对 HA 的有限交叉反应性 ADP。需要新的流感疫苗接种策略来引发交叉反应性和多功能抗体。
