Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12-15 months: A phase III, randomized, non-inferiority trial The MMR-161 Study Group

Por: Ahonen, A, Berry, A, Chatterjee, A, Clifford, R, Perez, C, Diez-Domingo, J, Haney, B, Harrison, C, Kerdpanich, A, Lee, J, Leonardi, M, Martinon-Torres, F, Miranda, M, Porcuna, X, Phongsamart, W, Huda, E, Toh, T, Twiggs, J, Arminana, A, Varman, M, Zissman, E, Caplanusi, A, Carryn, S, Henry, O, Povey, M and MMR-161 Study Grp

Publicada: 11 sep 2018
Background: The potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation. Methods: In this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMRRIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and antimumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT). Results: Each formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (-10.94%) was beyond the pre-defined limit of -10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles. Conclusions: One dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a non-inferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-year-old children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups. (C) 2018 Published by Elsevier Ltd.

Ahonen, A: Univ Tampere, Vaccine Res Ctr, Tampere, Finland
Berry, A: Univ Maryland, Sch Med, Ctr Vaccine Dev, Inst Global Hlth, Baltimore, MD 21201 USA
Chatterjee, A: Univ South Dakota, Sanford Sch Med, Sanford Childrens Specialty Clin, Dept Pediat, Sioux Falls, SD USA
Clifford, R: Coastal Pediat Associates, Charleston, SC USA
Perez, CD: Univ Puerto Rico, Sch Med, Med Sci Campus, San Juan, PR 00936 USA
Diez-Domingo, J: Ctr Super Invest Salud Publ, Valencia, Spain
Haney, B: Ellensburg & Pacific Northwest Univ, Family Hlth Care Ellensburg, Ellensburg, WA USA
Harrison, CJ: Childrens Mercy Hosp & Clin, Kansas City, MO USA
Kerdpanich, AP: Phramongkutklao Hosp, Dept Pediat, Div Infect Dis, Bangkok, Thailand
Lee, JKF: Hosp Sultanah Nur Zahirah, Kuala Terengganu, Malaysia
Leonardi, M: Palmetto Pediat, N Charleston, SC USA
Martinon-Torres, F: Hosp Clin Univ, Santiago De Compostela, Spain
Miranda, M: Hosp Antequera, Pediat Dept, Antequera, Spain
Porcuna, XMP: Manlleu Primary Care Ctr, Manlleu, Spain
Phongsamart, W: Madiol Univ, Siriraj Hosp, Fac Med, Pediat Infect Dis Unit,Dept Pediat, Bangkok, Thailand
Huda, EAS: Hosp Sultanah Nur Zahirah, Kuala Terengganu, Malaysia
Toh, TH: Sibu Hosp, Dept Pediat, Sibu, Sarawak, Malaysia; Sibu Hosp, Clin Res Ctr, Sibu, Sarawak, Malaysia
Twiggs, J: Dixie Pediat, St George, UT USA
Arminana, AU: EBA Centelles, Ctr Atencio Primaria, Barcelona, Spain
Varman, M: Creighton Univ, Pediat Infect Dis, Omaha, NE 68178 USA
Zissman, E: Childrens Res, Altamonte Springs, FL USA
Caplanusi, A: GSK, Wavre, Belgium
Carryn, S: GSK, Wavre, Belgium
Henry, O: GSK, Rockville, MD USA
Povey, M: GSK, Wavre, Belgium
ISSN: 13588745

Tipo de documento: Article
Volumen: 36 Número: 38
Páginas: 5781-5788s
WOS: 000445984000016