Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 191, Issue 7, Pages 1093-1104Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/427813
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Funding
- NIAID NIH HHS [N01-AI-15444] Funding Source: Medline
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Background. Recombination technology can be used to create live attenuated respiratory syncytial virus (RSV) vaccines that contain combinations of known attenuating mutations. Methods. Two live attenuated, recombinantly derived RSV vaccine candidates, rA2cp248/404DeltaSH and rA2cp248/404/1030DeltaSH, were evaluated in 31 adults and in 95 children greater than or equal to6 months old. rA2cp248/404/1030DeltaSH was subsequently evaluated in 44 infants 1 - 2 months old. These vaccine candidates share 4 attenuating genetic elements and differ only in a missense mutation ( 1030) in the polymerase gene. Results. Both vaccines were highly attenuated in adults and RSV-seropositive children and were well tolerated and immunogenic in RSV-seronegative children. Compared with that of rA2cp248/404DeltaSH, replication of rA2cp248/404/1030DeltaSH was restricted in RSV-seronegative children (mean peak titer, 10(4.3) vs. 10(2.)5 plaque-forming units [pfu]/mL), indicating that the 1030 mutation had a potent attenuating effect. Although rA2cp248/404/ 1030DeltaSH was well tolerated in infants, only 44% of infants who received two 10(5.3)-pfu doses of vaccine had detectable antibody responses. However, replication after administration of the second dose was highly restricted, indicating that protective immunity was induced. At least 4 of 5 attenuating genetic elements were retained in recovered vaccine viruses. Conclusions. rA2cp248/404/1030DeltaSH is the first RSV vaccine candidate to be sufficiently attenuated in young infants. Additional studies are needed to determine whether rA2cp248/404/1030DeltaSH can induce protective immunity against wild-type RSV.
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