A high dose of IMT504, the PyNTTTTGT prototype immunostimulatory oligonucleotide, does not alter embryonic development in rats.
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.
Hernando-Insúa
Andrés
A
Immunotech S.A, Buenos Aires, Argentina.
Rodriguez
Juan M
JM
Elías
Fernanda
F
Fló
Juan
J
López
Ricardo
R
Franco
Raul
R
Lago
Nestor
N
Zorzopulos
Jorge
J
Montaner
Alejandro D
AD
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats; D017207:Rats, Sprague-Dawley
C514285:IMT504; D009838:Oligodeoxyribonucleotides