TY - JOUR
T1 - Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine
T2 - Early results from a randomised controlled trial
AU - Ren, Shu
AU - Hansbro, Philip M.
AU - Srikusalanukul, Wichat
AU - Horvat, Jay C.
AU - Hunter, Tegan
AU - Brown, Alexandra C.
AU - Peel, Roseanne
AU - Faulkner, Jack
AU - Evans, Tiffany Jane
AU - Li, Shu Chuen
AU - Newby, David
AU - Hure, Alexis
AU - Abhayaratna, Walter P.
AU - Tsimikas, Sotirios
AU - Gonen, Ayelet
AU - Witztum, Joseph L.
AU - Attia, John
AU - Abhayaratna, Walter
AU - D'Este, Catherine
AU - Tonkin, Andrew
AU - Hopper, Ingrid
AU - Thrift, Amanda
AU - Levi, Christopher
AU - Sturm, Jonathan
AU - Durrheim, David
AU - Hung, Joseph
AU - Briffa, Tom
AU - Chew, Derek
AU - Anderson, Phil
AU - Moon, Lynelle
AU - McEvoy, Mark
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - Background and aims: 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. Methods: 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). Results: 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. Conclusions: 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.
AB - Background and aims: 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. Methods: 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). Results: 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. Conclusions: 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.
KW - Anti-oxLDL antibodies
KW - Anti-pneumococcal antibodies
KW - Atherosclerosis
KW - Cardiovascular disease
KW - Human clinical trial
KW - Oxidative stress
KW - Pneumococcal vaccine
UR - http://www.scopus.com/inward/record.url?scp=85126085765&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2022.02.011
DO - 10.1016/j.atherosclerosis.2022.02.011
M3 - Article
SN - 0021-9150
VL - 346
SP - 68
EP - 74
JO - Atherosclerosis
JF - Atherosclerosis
ER -