Feasibilty of in utero DNA vaccination following naked gene transfer into pig fetal muscle: transgene expression, immunity and safety.
The high toll of death among first-week infants is due to infections occurring at the end of pregnancy, during birth or by breastfeeding. This problem significantly concerns industrialized countries also. To prevent the typical "first-week infections", a vaccine would be protective as early as at the birth. In utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. We have already published results of a 2-year follow-up showing long-term safety, protective antibody titers at birth and long-term immune memory, following intramuscular in utero anti-HBV DNA immunization in 90-days pig fetuses. We have now analyzed further parameters of short-term safety. Two different reporter genes were injected in the thigh muscles of 90-days fetuses. At 8 days following DNA injection, we found high-level of transgenes expression in all injected fetuses. A step gradient of expression from the area of injection was observed with both reporter genes. CMV promoter/enhancer produced higher levels of expression compared to SV40 promoter/enhancer. Moreover, no evidence of local or systemic flogistic alterations or fetal malformations, mortality or haemorrhage following intramuscular injection were observed. A single anti-HBV s-antigen DNA immunization in 90-days fetuses supported protective antibody levels in all immunized newborns, lasting at least up to 4 months after birth. Our report further sustains safety and efficacy of intramuscular in utero naked gene transfer and immunization. This approach may support therapeutic or prophylactic procedure in many early life-threatening pathologic conditions.
Rinaldi
Monica
M
Institute of Neurobiology and Molecular Medicine, CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy.
Signori
Emanuela
E
Rosati
Paolo
P
Cannelli
Giorgio
G
Parrella
Paola
P
Iannace
Enrico
E
Monego
Giovanni
G
Ciafrè
Silvia Anna
SA
Farace
Maria Giulia
MG
Iurescia
Sandra
S
Fioretti
Daniela
D
Rasi
Guido
G
Fazio
Vito Michele
VM
D000818:Animals; D005240:Feasibility Studies; D005260:Female; D018014:Gene Transfer Techniques; D009132:Muscles / Q000196:embryology*; D010957:Plasmids; D011247:Pregnancy; D013552:Swine / Q000196:embryology*; D019076:Transgenes; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D019444:Vaccines, DNA