Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial

Stanek, 2012, Lyme borreliosis, Lancet, 379, 461, 10.1016/S0140-6736(11)60103-7 Steere, 2012, Lyme disease vaccines, 1122 Stanek, 2011, Lyme borreliosis: clinical case definitions for diagnosis and management in Europe, Clin Microbiol Infect, 17, 69, 10.1111/j.1469-0691.2010.03175.x Plotkin, 2011, Correcting a public health fiasco: the need for a new vaccine against Lyme disease, Clin Infect Dis, 52, s271, 10.1093/cid/ciq119 Nadelman, 2012, Differentiation of reinfection from relapse in recurrent Lyme disease, N Engl J Med, 367, 1883, 10.1056/NEJMoa1114362 Rizzoli, 2011, Lyme borreliosis in Europe, Euro Surveill, 16, 19906, 10.2807/ese.16.27.19906-en 2012, Notices to readers: final 2011 reports of nationally notifiable infectious diseases, MMWR Morb Mortal Wkly Rep, 61, 624 Lindgren Sigal, 1998, A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease, N Engl J Med, 339, 216, 10.1056/NEJM199807233390402 Steere, 1998, Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant, N Engl J Med, 339, 209, 10.1056/NEJM199807233390401 Gross, 1998, Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis, Science, 281, 703, 10.1126/science.281.5377.703 Poland, 2011, Vaccines against Lyme disease: what happened and what lessons can we learn?, Clin Infect Dis, 52, s253, 10.1093/cid/ciq116 Steere, 2011, Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis, Clin Infect Dis, 52, s259, 10.1093/cid/ciq117 Ding, 2000, Structural identification of a key protective B-cell epitope in Lyme disease antigen OspA, J Mol Biol, 302, 1153, 10.1006/jmbi.2000.4119 Luft, 2002, Approaches toward the directed design of a vaccine against Borrelia burgdorferi, J Infect Dis, 185, S46, 10.1086/338463 Livey, 2011, A new approach to a Lyme disease vaccine, Clin Infect Dis, 52, s266, 10.1093/cid/ciq118 Drouin, 2004, Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato, J Autoimmun, 23, 281, 10.1016/j.jaut.2004.06.005 Liang, 1999, Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi vlsE, J Clin Microbiol, 37, 3990, 10.1128/JCM.37.12.3990-3996.1999 Hanley, 1983, If nothing goes wrong, is everything all right? Interpreting zero numerators, JAMA, 249, 1743, 10.1001/jama.1983.03330370053031 Aichinger, 2011, Safety and immunogenicity of an inactivated whole virus Vero cell-derived Ross River virus vaccine: a randomized trial, Vaccine, 29, 9376, 10.1016/j.vaccine.2011.09.125 Ehrlich, 2008, A clinical trial of a whole-virus H5N1 vaccine derived from cell culture, N Engl J Med, 358, 2573, 10.1056/NEJMoa073121 Nicholson, 2001, Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza, Lancet, 357, 1937, 10.1016/S0140-6736(00)05066-2 Schoen, 2000, Safety and immunogenicity profile of a recombinant outer-surface protein A Lyme disease vaccine: clinical trial of a 3-dose schedule at 0, 1, and 2 months, Clin Ther, 22, 315, 10.1016/S0149-2918(00)80035-1 Van Hoecke, 1996, Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults, Vaccine, 14, 1620, 10.1016/S0264-410X(96)00146-6 Schoen, 2003, An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine, Clin Ther, 25, 210, 10.1016/S0149-2918(03)90027-0 Van Hoecke, 1998, Clinical and immunological assessment of a candidate Lyme disease vaccine in healthy adults: antibody persistence and effect of a booster dose at month 12, Vaccine, 16, 1688, 10.1016/S0264-410X(98)00052-8 Van Hoecke, 1999, Alternative vaccination schedules (0, 1, and 6 months versus 0, 1, and 12 months) for a recombinant OspA Lyme disease vaccine, Clin Infect Dis, 28, 1260, 10.1086/514779 Hirschfeld, 1999, Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2, J Immunol, 163, 2382, 10.4049/jimmunol.163.5.2382 Keller, 1994, Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine, JAMA, 271, 1764, 10.1001/jama.1994.03510460056033 Lindblad, 2004, Aluminium adjuvants—in retrospect and prospect, Vaccine, 22, 3658, 10.1016/j.vaccine.2004.03.032 Alexopoulou, 2002, Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice, Nat Med, 8, 878, 10.1038/nm732 HogenEsch, 2002, Mechanisms of stimulation of the immune response by aluminum adjuvants, Vaccine, 20, S34, 10.1016/S0264-410X(02)00169-X Stills, 2005, Adjuvants and antibody production: dispelling the myths associated with Freund's complete and other adjuvants, ILAR J, 46, 280, 10.1093/ilar.46.3.280 Sikand, 2001, Safety and immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against lyme disease in healthy children and adolescents: a randomized controlled trial, Pediatrics, 108, 123, 10.1542/peds.108.1.123 Schoen, 1995, Safety and immunogenicity of an outer surface protein A vaccine in subjects with previous Lyme disease, J Infect Dis, 172, 1324, 10.1093/infdis/172.5.1324 Plotkin, 2010, Correlates of protection induced by vaccination, Clin Vaccine Immunol, 17, 1055, 10.1128/CVI.00131-10 Coleman, 1997, Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice, Cell, 89, 1111, 10.1016/S0092-8674(00)80298-6 Pal, 2001, Inhibition of Borrelia burgdorferi-tick interactions in vivo by outer surface protein A antibody, J Immunol, 166, 7398, 10.4049/jimmunol.166.12.7398 Battisti, 2008, Outer surface protein A protects Lyme disease spirochetes from acquired host immunity in the tick vector, Infect Immun, 76, 5228, 10.1128/IAI.00410-08 Feder, 1999, Immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against Lyme disease in children, J Pediatr, 135, 575, 10.1016/S0022-3476(99)70055-7