Publication

Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children

Two candidate vaccines attenuated by M2-2 deletion, MEDI/∆M2-2 and LID/∆M2-2, have recently been evaluated. These 2 candidates were derived from 2 different recombinant parental complementary DNAs (cDNAs) that differ by 21 nucleotide assignments scattered through the genome, including 2 coding changes in the N2 and N ORFs. The candidates also differ in the design of the M2-2 deletion, and LID/∆M2-2 has a 112-nucleotide deletion and silent mutations in the small hydrophobic (SH) gene and the SH ORF introduced to improve the stability of the cDNA during growth in bacteria. The 2 vaccines had similar phenotypes in vitro and in animals. When administered to RSV-seronegative children (ages 6–24 months), both vaccines induced strong RSV-neutralizing antibody responses in a large proportion of vaccinees and demonstrated anamnestic antibody responses after wild-type RSV exposure; however, the peak titer of vaccine virus shed in nasal wash (NW) specimens was approximately 100-fold lower for MEDI/∆M2-2. Thus, these modest genetic differences apparently contributed to a different replication phenotype in children.