Ren Shu, Hansbro Philip M, Srikusalanukul Wichat, Horvat Jay C, Hunter Tegan, Brown Alexandra C, Peel Roseanne, Faulkner Jack, Evans Tiffany-Jane, Li Shu Chuen, Newby David, Hure Alexis, Abhayaratna Walter P, Tsimikas Sotirios, Gonen Ayelet, Witztum Joseph L, Attia John
School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; Centenary UTS Centre for Inflammation, Sydney, NSW, Australia.
Atherosclerosis. 2022 Apr;346:68-74. doi: 10.1016/j.atherosclerosis.2022.02.011. Epub 2022 Mar 5.
Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years.
A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH).
Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up.
PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.
观察性研究表明，肺炎球菌多糖疫苗（PPV）与心血管事件风险降低相关。这可能是通过抗氧化型低密度脂蛋白（OxLDL）的IgM抗体介导的，此前已发现该抗体具有心脏保护作用。澳大利亚心血管事件免疫预防研究（AUSPICE）是一项关于PPV预防缺血性事件的双盲随机对照试验（RCT）。参与者在基线时接受一次PPV或安慰剂注射，并在6年期间接受致命和非致命心肌梗死或中风事件的随访。
在一个中心（堪培拉；n = 1001）的一组参与者在免疫接种后1个月和2年进行评估，以观察动脉粥样硬化替代标志物的变化，作为预先设定的次要结局：高敏C反应蛋白（CRP）、脉搏波速度（PWV）和颈动脉内膜中层厚度（CIMT）。此外，在干预组和对照组中各随机选择100名参与者，测量抗肺炎球菌抗体（IgG、IgG2、IgM）以及抗OxLDL抗体（抗铜氧化修饰低密度脂蛋白、丙二醛修饰低密度脂蛋白和磷酸胆碱-钥孔戚血蓝蛋白的IgG和IgM）。
与安慰剂组相比，PPV组抗肺炎球菌IgG和IgG2浓度在2年时升高并维持在较高水平，而IgM浓度在2年时先升高后下降，但仍可检测到。所有抗OxLDL IgM抗体在1个月时均有统计学意义的升高，在2年时不再可检测到；抗OxLDL IgG抗体无升高。在2年随访时，治疗组之间CRP、PWV或CIMT无显著变化。
PPV可使抗肺炎球菌IgG水平长期升高，抗IgM水平升高程度较小，同时抗OxLDL IgM抗体短暂升高。然而，在2年随访时，动脉粥样硬化替代标志物未发现可检测到的变化。对临床结局的长期前瞻性随访仍在继续，以评估PPV是否能降低心血管疾病事件。
