Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated.

Related People: Ruth A. Karron, MD
Related Research: RSV
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The RSV vaccine candidate LIDcp∆M2-2 is overattenuated and not suitable for further development. A  related product, LID∆M2-2, was previously shown to have excellent infectivity and immunogenicity in RSV-seronegative children aged 6–24  months, inducing 4-fold increases in serum RSV neutralizing antibodies in 90% of vaccinees. The cp mutations were added with the expectation of slightly reducing the level of replication of LID∆M2-2. However, the results of the present study suggest that adding the additional 5 cp mutations significantly increased attenuation, exceeding the moderately restrictive effects observed in preclinical studies and resulting in a candidate vaccine with suboptimal vaccine take and immunogenicity. In preclinical studies in African Green Monkeys, LIDcpΔM2-2 at doses of 1 and 2 × 106 PFU demonstrated low or undetectable levels of replicating virus and excellent antibody responses (Investigator’s Brochure, version 29 July 2016). Cold-passaged RSV was originally derived by 52 sequential cell culture passages at low temperatures. Earlier studies of cpRSV demonstrated that the vaccine was underattenuated, and subsequent studies evaluating cpRSV with additional attenuating mutations have shown over- or underattenuation.

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