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Vaccine Detail

LID/ΔM2-2/1030s
Vaccine Information
  • Vaccine Name: LID/ΔM2-2/1030s
  • Target Pathogen: Human Respiratory Syncytial Virus
  • Target Disease: Respiratory tract disease
  • Manufacturer: Charles River Laboratories Malvern, PA
  • Type: Live, attenuated vaccine
  • Status: Clinical trial
  • Host Species for Licensed Use: None
  • M2-2 gene engineering:
    • Type: Recombinant protein preparation
    • Description: 241 deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 (McFarland et al., 2020).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2 with 241 nts deleted from the M2-2 ORF and the 3 potential translation initiation codons of the M2-2 ORF silenced (McFarland et al., 2020).
Host Response

Human Response

  • Host age: (Endt et al., 2022)Children 6-24 months
  • Vaccination Protocol: (McFarland et al., 2020)Eligible children were RSV seronegative at screening, defined as having a complement-enhanced serum RSV 60% plaque reduction neutralizing titer. Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.
  • Challenge Protocol: (McFarland et al., 2020)The small sample size precludes firm estimates of rates of vaccine-associated events, infectivity, immunogenicity, and viral replication.
  • Efficacy: (McFarland et al., 2020)Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.
  • Description: The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2. The results showed that the LID/∆M2-2/1030s is a very attractive candidate for further development as a live attenuated in trans Al pediatric RSV vaccine.
References
Endt et al., 2022: Endt K, Wollmann Y, Haug J, Bernig C, Feigl M, Heiseke A, Kalla M, Hochrein H, Suter M, Chaplin P, Volkmann A. A Recombinant MVA-Based RSV Vaccine Induces T-Cell and Antibody Responses That Cooperate in the Protection Against RSV Infection. Frontiers in immunology. 2022; 13; 841471. [PubMed: 35774800].
McFarland et al., 2020: McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, Collins P, Buchholz UJ. Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. The Journal of infectious diseases. 2020; 221(4); 534-543. [PubMed: 31758177].