Smallpox Vaccination Does Not Elevate Systemic Levels of Prothrombotic Proteins Associated with Ischemic Cardiac Events

Shaklee, Julia; Talbot, Thomas R.; Muldowney, James A.S.; Vaughan, Douglas E.; Butler, Javed; House, Frances S.; Crowe, James E.; Smith, Layton H.; Edwards, Kathryn M.

doi:10.1086/427831

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…Both trials were conducted at Vanderbilt University in the NIH-funded Vaccine and Treatment Evaluation Unit (VTEU) [4,8,11]. The first study [7] enrolled 85 healthy vaccinia-naïve adults in genotyping studies and the second study [11] also enrolled 46 healthy vaccinia-naïve adults. In both studies, individuals were asked to self-identify ethnic background.…”

Section: Methodsmentioning

confidence: 99%

Genetic Basis for Adverse Events after Smallpox Vaccination

et al. 2008

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Background Although vaccinia immunization is highly effective in preventing smallpox, post-vaccination reactions are common. Identifying genetic factors associated with AEs might allow screening before vaccinia administration and provide a rational basis for the development of improved vaccine candidates. Methods Two independent clinical trials in healthy, vaccinia-naïve adult volunteers were conducted with the Aventis Pasteur smallpox vaccine (APSV). Volunteers were assessed repeatedly for local and systemic AEs to vaccine and were genotyped using the same panel of 1442 single-nucleotide polymorphisms (SNPs). Results In the first study, thirty-six SNPs in 26 genes were associated with systemic AEs (p-value ≤ 0.05). In the second study, only those SNPs associated with AEs in the first sample were tested. In the final analysis, three SNPs were associated consistently with AEs in both studies. A nonsynonymous SNP in methylenetetrahydrofolate reductase (MTHFR) was associated with AE risk in both trials (odds ratio [OR]; 95% confidence interval [CI]); p-value [p]): (OR=2.3; CI=1.1–5.2; p=0.04) and (OR=4.1; CI=1.4–11.4; p<0.01). Two SNPs in the interferon regulatory factor 1 (IRF1) gene were associated with AE risk in both sample sets: (OR=3.2; CI=1.1–9.8; p=0.03) and (OR=3.0; CI=1.1–8.3; p=0.03). Conclusions Genetic polymorphisms in an enzyme previously associated with adverse reactions to a variety of pharmacologic agents (MTHFR) and an immunological transcription factor (IRF1) were associated with AEs after smallpox vaccination in two independent study samples. These findings highlight common genetic variants with promising clinical significance that merit further investigation.

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Section: Methodsmentioning

confidence: 99%

Genetic Basis for Adverse Events after Smallpox Vaccination

et al. 2008

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Pox, patient, and plaque

Murphy

Wright

2008

Vaccine

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The first steps towards the era of personalised vaccinology: predicting adverse reactions

et al. 2014

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Until now, the occurrence of adverse reactions among individuals inoculated with identical vaccines has been ascribed to unpredictable stochastic processes. Recent advances in pharmacogenomics indicate that some features of host response to immunisation are influenced by genetic traits, henceforth predictable. The ability to predict the adverse reaction to vaccination would represent an important step towards the development of personalised vaccinology and could enhance public confidence in the safety of vaccines. Herein, we have reviewed all the available information on the association between genetic variants and the risk for healthy subjects to develop adverse reactions.

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Smallpox Vaccination Does Not Elevate Systemic Levels of Prothrombotic Proteins Associated with Ischemic Cardiac Events

Abstract: Levels of PAI-1 and sCD40L did not significantly increase after smallpox vaccination. Vaccine-induced alterations in levels of these prothrombotic proteins do not appear to play a role in ischemic events observed after smallpox vaccination.

Cited by 3 publications

References 19 publications

Genetic Basis for Adverse Events after Smallpox Vaccination

Genetic Basis for Adverse Events after Smallpox Vaccination

Pox, patient, and plaque

The first steps towards the era of personalised vaccinology: predicting adverse reactions

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