A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children

作者：Karron Ruth A^*; Luongo Cindy; Thumar Bhagvanji; Loehr Karen M; Englund Janet A; Collins Peter L; Buchholz Ursula J

来源：Science Translational Medicine, 2015, 7(312): 312ra175.

DOI：10.1126/scitranslmed.aac8463

Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and a safe and effective vaccine for use in infancy and early childhood is needed. We previously showed that deletion of the coding sequence for the viral M2-2 protein (Delta M2-2) down-regulated viral RNA replication and up-regulated gene transcription and antigen synthesis, raising the possibility of development of an attenuated vaccine with enhanced immunogenicity. RSV MEDI DM2-2 was therefore evaluated as a live intranasal vaccine in adults, RSV-seropositive children, and RSV-seronegative children. When results in RSV-seronegative children were compared to those achieved with the previous leading live attenuated RSV candidate vaccine, vaccine virus shedding was significantly more restricted, yet the post-vaccination RSV-neutralizing serum antibody achieved [geometric mean titer (GMT) = 1: 97] was significantly greater. Surveillance during the subsequent RSV season showed that several seronegative RSV MEDI DM2-2 recipients had substantial antibody rises without reported illness, suggesting that the vaccine was protective yet primed for anamnestic responses to RSV. Rational design appears to have yielded a candidate RSV vaccine that is intrinsically superior at eliciting protective antibody in RSV-naive children and highlights an approach for the development of live attenuated RSV vaccines.

• 出版日期2015-11-4