A high dose of IMT504, the PyNTTTTGT prototype immunostimulatory oligonucleotide, does not alter embryonic development in rats

Oligonucleotides
Andrés Hernando-InsúaAlejandro D Montaner

Abstract

Synthetic oligodeoxynucleotides (ODNs) are currently being evaluated as vaccine adjuvants for inducing protective immunity. As maternal vaccination is becoming increasingly common, the potential risk of vaccine formulation using ODN adjuvants should be warranted. A recent study performed in mice suggests that exposure to CpG motifs during pregnancy could result (although at very high doses as compared to the ones proposed for human vaccination) in fetal loss and morphological defects. PyNTTTTGT ODNs are immunostimulatory ODNs not bearing CpG motifs, which are very efficient vaccine adjuvants. In this report, we analyzed the potential teratogenic effect of its prototype IMT504 in rats. This animal model was chosen because PyNTTTTGT ODNs are barely active in mice. Intraperitoneal injection of IMT504 at a dose of 20 mg/kg (more than 1000 times higher than the one proposed for a vaccine dose in humans) at day 6 of pregnancy did not produce a significant decrease in the mean number of implanted fetuses or in the number of live pups delivered. Neither the fetuses nor the offspring presented malformations.

References

Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fernanda EliasJuan M Rodriguez
Aug 21, 2007·Expert Opinion on Biological Therapy·Yanal M MuradMichael A Morse
Nov 21, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marion Jurk, Jörg Vollmer
Jul 26, 2008·Current Opinion in Immunology·Winfried BarchetGunther Hartmann
Aug 2, 2008·Neuroscience Letters·María Florencia CoronelMarcelo José Villar

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Citations

Apr 12, 2014·Nucleic Acid Therapeutics·Raúl FrancoAlejandro D Montaner
Jul 13, 2014·Human Reproduction Update·Azure N FaucetteKang Chen
Jun 23, 2016·American Journal of Physiology. Endocrinology and Metabolism·María S BianchiVictoria A Lux-Lantos

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Methods Mentioned

BETA
Flow Cytometry
Fluorescence

Software Mentioned

Win MDI

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