Studies On Protective Effects Of Maternal Antibodies Induced By CMV Vaccine In Mouse Offspring

Human cytomegalovirus?HCMV?is the most frequent cause of congenital viral infection.The clinical manifestations in symptomatic infants include microcephaly and neurodevelopmental injury.Neonatal infection with the virus also easily resulted in hepatitis,pneumonitis and biliary atresia.CMV-specific antibodies in the fetal bloodstream from maternal circulation could suppress the viral replication in the placenta and prevent congenital disease.Researches proved that vaccination of women before and during pregnancy can induce or increase the concentration of specific Ig G antibodies to protect the offspring.At present,there is still no licensed HCMV vaccine worldwide to defend the infection.Our previous study showed that inactivated murine cytomegalovirus?MCMV?vaccine could provide protection for mice against lethal virus challenge.In this study,we explored the protective abilities in offspring provided by maternal immunization of mice with inactivated MCMV vaccine.The study consisted of two parts.1)Protection of offspring by maternal antibody induced by inactivated vaccine alone or with MF59 Female Balb/c mice aged 7-8 weeks were immunized twice with1?g or 4?g of inactivated MCMV vaccine alone or adjuvanted with MF59.One week after the second immunization,they were mated with unimmunized male mice.Their offspring were grouped and challenged with a lethal dose of MCMV virus at different ages.The result showed that the offspring from mice immunized with 1?g or 4?g of inactivated vaccine alone could not be protected by the maternal antibody against the lethal challenge.They all died within 7 days postchallenge.When mothers were immunized with 1?g of vaccine plus MF59,their offspring had a survival rate of 87.5%?50%and 0%at age of 2,3 and 4 weeks,respectively.When mothers were immunized with 4?g of vaccine plus MF59,their offspring had a survival rate of 100%?100%and 87.5%at age of 2,3 and 4 weeks,respectively,and the maternal antibody levels in offspring were still high(2^9.3)at age of 8 weeks.2)Protection of offspring by maternal antibody transferred through different routes Female Balb/c mice aged 7-8 weeks were unimmunized or immunized twice with 4?g of inactivated MCMV vaccine adjuvanted with MF59.One week after the second immunization,they were mated with unimmunized male mice.After birth,the offspring from unimmunized and immunized mothers were cross-fostered by immunized and unimmunized mothers,respectively,and were challenged with a lethal dose of virus at different ages.The maternal antibody passed through breastfeeding protected the offspring against the challenge with a survival rate of 100%?100%and 75%at age of 2,3 and 4 weeks,respectively,and the antibody levels in offspring were still high(2^7.5)at age of 8 weeks.By contrast,the maternal antibody passed through placenta could not protect the offspring against the challenge.They all died within 7 days postchallenge.At age of 8 weeks the levels of maternal antibody passed through placenta were very low(2^4.3).The experiments demonstrated that mice immunized with inactivated vaccine adjuvanted with MF59 could effectively protect their offspring against a lethal dose of MCMV challenge,and that the maternal antibody was mainly transferred by milk to the offspring in providing protection.The study would give useful references for HCMV vaccine research and for prevention of congenital HCMV infection.