Vaccination in utero may cut vertical transmission

Vaccination in utero may reduce the vertical transmission of infectious diseases. Canadian scientists have introduced a DNA herpes vaccine into the amniotic fluid of fetal lambs and elicited a powerful immune response to it. Their hope is that this approach may eventually reduce the need for caesarean sections in women at high risk of passing on infections such as herpes and hepatitis to their offspring (Nature Medicine 2000;6:929-32).

Dr Philip Griebel and his team at the Veterinary Infectious Disease Organisation, University of Saskatchewan, sought to develop a DNA vaccine for use in utero that could protect against perinatal infectious diseases - a treatment that would be compatible with the technology already in use, such as amniocentesis. They chose the herpes vaccine because they had used it in previous research, and they chose lambs because their immune system functions are similar to those of humans.

DNA vaccines consist of small non-pathological sequences of naked DNA encoding a single gene from a specific pathogen. No carrier agent is required, and the DNA does not become integrated into the host's cells, making it a safe procedure. Dr Griebel's team introduced the herpes vaccine directly into the mouths of third trimester fetal lambs by making a small insertion into the abdomen, locating the head of the fetus and passing a needle through the uterine wall and positioning it in the fetus's mouth. Just before birth, the team sought evidence of systemic immunity by looking for specific serum antibodies and for evidence of local mucosal immunity in the form of antigen specific cells in the lymphoid tissue around the mouth.

Mucosal immunity is important because most infectious agents enter newborns through mucosal tissue. All lambs tested in this way showed a strong immune response. Dr Griebel confirmed that the antibodies produced by all these animals are capable of neutralising antigen in vitro, but he has not yet carried out a disease challenge in any neonatal animals vaccinated in this way. He expects that a perinatal booster will also be required, as with most immunisation processes, and that the process in humans will be made technically easier by the use of ultrasound to guide the vaccine needle into the fetal oral cavity. Further work is needed to ascertain the best time for vaccination in utero to minimise any risk to mother and fetus, while still achieving a protective immune response. "This work challenges the view that neonates are not immune competent at birth," said Dr Griebel.