The emerging field of oncolytic virus-based cancer immunotherapy
Tài liệu tham khảo
Poh, 2016, First oncolytic viral therapy for melanoma, Cancer Discov., 6, 6, 10.1158/2159-8290.CD-NB2015-158
Todo, 2022, Intratumoral oncolytic herpes virus G47Δ for residual or recurrent glioblastoma: a phase 2 trial, Nat. Med., 28, 1630, 10.1038/s41591-022-01897-x
Kaufman, 2015, Oncolytic viruses: a new class of immunotherapy drugs, Nat. Rev. Drug Discov., 14, 642, 10.1038/nrd4663
Haseley, 2009, Advances in oncolytic virus therapy for glioma, Recent Pat. CNS Drug Discov., 4, 1, 10.2174/157488909787002573
Tremaglio, 2021, Genetic instability of RNA viruses, 23
Msaouel, 2013, Oncolytic measles virus strains as novel anticancer agents, Expert. Opin. Biol. Ther., 13, 483, 10.1517/14712598.2013.749851
Chiocca, 2002, Oncolytic viruses, Nat. Rev. Cancer, 2, 938, 10.1038/nrc948
Kambara, 2005, An oncolytic HSV-1 mutant expressing ICP34.5 under control of a nestin promoter increases survival of animals even when symptomatic from a brain tumor, Cancer Res., 65, 2832, 10.1158/0008-5472.CAN-04-3227
Mazzacurati, 2015, Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV, Mol. Ther., 23, 99, 10.1038/mt.2014.177
Xia, 2016, Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis, Cancer Res., 76, 6747, 10.1158/0008-5472.CAN-16-1404
Xia, 2016, Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis, Cell Rep., 14, 282, 10.1016/j.celrep.2015.12.029
Lipatova, 2021, Multi-omics analysis of glioblastoma cells' sensitivity to oncolytic viruses, Cancers (Basel), 13, 5268, 10.3390/cancers13215268
Seymour, 2016, Oncolytic viruses: finally delivering, Br. J. Cancer, 114, 357, 10.1038/bjc.2015.481
Buijs, 2015, Oncolytic viruses: from bench to bedside with a focus on safety, Hum. Vaccin. Immunother., 11, 1573, 10.1080/21645515.2015.1037058
Martinez-Quintanilla, 2019, Oncolytic viruses: overcoming translational challenges, J. Clin. Invest., 129, 1407, 10.1172/JCI122287
Sathaiah, 2012, Oncolytic poxvirus armed with Fas ligand leads to induction of cellular Fas receptor and selective viral replication in FasR-negative cancer, Cancer Gene Ther., 19, 192, 10.1038/cgt.2011.77
Gaddy, 2007, Oncolytic vesicular stomatitis virus induces apoptosis via signaling through PKR, Fas, and Daxx, J. Virol., 81, 2792, 10.1128/JVI.01760-06
Paul, 2017, The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy, Front. Immunol., 8, 1124, 10.3389/fimmu.2017.01124
Saha, 2017, Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade, Cancer Cell, 32, 253, 10.1016/j.ccell.2017.07.006
Zhang, 2022, Oncolytic adenoviruses synergistically enhance anti-PD-L1 and anti-CTLA-4 immunotherapy by modulating the tumour microenvironment in a 4T1 orthotopic mouse model, Cancer Gene Ther., 29, 456, 10.1038/s41417-021-00389-3
Ma, 2020, Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer, Cell Death Dis., 11, 48, 10.1038/s41419-020-2236-3
Li, 2022, ILC1s control leukemia stem cell fate and limit development of AML, Nat. Immunol., 23, 718, 10.1038/s41590-022-01198-y
Kansler, 2022, Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies, Nat. Immunol., 23, 904, 10.1038/s41590-022-01213-2
Serafini, 2022, Trained ILC3 responses promote intestinal defense, Science, 375, 859, 10.1126/science.aaz8777
Melcher, 2021, Oncolytic virotherapy as immunotherapy, Science, 374, 1325, 10.1126/science.abk3436
Kaufman, 2005, Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma, J. Clin. Invest., 115, 1903, 10.1172/JCI24624
Ribas, 2017, Oncolytic virotherapy promotes intratumoral T cell infiltration and improves Anti-PD-1 immunotherapy, Cell, 170, 1109, 10.1016/j.cell.2017.08.027
Dimitriou, 2022, Double trouble: immunotherapy doublets in melanoma – approved and novel combinations to optimize treatment in advanced melanoma, Am. Soc. Clin. Oncol. Educ. Book, 1
Conry, 2018, Talimogene laherparepvec: first in class oncolytic virotherapy, Hum. Vaccin. Immunother., 14, 839, 10.1080/21645515.2017.1412896
Liang, 2018, Oncorine, the world first oncolytic virus medicine and its update in China, Curr. Cancer Drug Targets, 18, 171, 10.2174/1568009618666171129221503
Xia, 2004, Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus, Ai Zheng, 23, 1666
Pecora, 2002, Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers, J. Clin. Oncol., 20, 2251, 10.1200/JCO.2002.08.042
Liu, 2022, Oncolytic adenovirus-mediated intratumoral expression of TRAIL and CD40L enhances immunotherapy by modulating the tumor microenvironment in immunocompetent mouse models, Cancer Lett., 535, 10.1016/j.canlet.2022.215661
Passaro, 2019, Arming an oncolytic herpes simplex virus type 1 with a single-chain fragment variable antibody against PD-1 for experimental glioblastoma therapy, Clin. Cancer Res., 25, 290, 10.1158/1078-0432.CCR-18-2311
Xu, 2021, An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma, Nat. Commun., 12, 5908, 10.1038/s41467-021-26003-6
Tian, 2022, Targeting Fc receptor-mediated effects and the 'don't eat me' signal with an oncolytic virus expressing an anti-CD47 antibody to treat metastatic ovarian cancer, Clin. Cancer Res., 28, 201, 10.1158/1078-0432.CCR-21-1248
Hellums, 2005, Increased efficacy of an interleukin-12-secreting herpes simplex virus in a syngeneic intracranial murine glioma model, Neuro-Oncology, 7, 213, 10.1215/S1152851705000074
Parker, 2000, Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors, Proc. Natl. Acad. Sci. U. S. A., 97, 2208, 10.1073/pnas.040557897
Saha, 2018, Combinatorial effects of VEGFR kinase inhibitor axitinib and oncolytic virotherapy in mouse and human glioblastoma stem-like cell models, Clin. Cancer Res., 24, 3409, 10.1158/1078-0432.CCR-17-1717
Chen, 2021, Intratumoral expression of interleukin 23 variants using oncolytic vaccinia virus elicit potent antitumor effects on multiple tumor models via tumor microenvironment modulation, Theranostics, 11, 6668, 10.7150/thno.56494
Pol, 2020, Cytokines in oncolytic virotherapy, Cytokine Growth Factor Rev., 56, 4, 10.1016/j.cytogfr.2020.10.007
Kowalsky, 2018, Superagonist IL-15-armed oncolytic virus elicits potent antitumor immunity and therapy that are enhanced with PD-1 blockade, Mol. Ther., 26, 2476, 10.1016/j.ymthe.2018.07.013
Ma, 2021, An oncolytic virus expressing IL15/IL15Rα combined with off-the-shelf EGFR-CAR NK cells targets glioblastoma, Cancer Res., 81, 3635, 10.1158/0008-5472.CAN-21-0035
Park, 2015, Phase 1b trial of biweekly intravenous Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus in colorectal cancer, Mol. Ther., 23, 1532, 10.1038/mt.2015.109
Yu, 2014, T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy, Mol. Ther., 22, 102, 10.1038/mt.2013.240
Fajardo, 2017, Oncolytic adenoviral delivery of an EGFR-targeting T-cell engager improves antitumor efficacy, Cancer Res., 77, 2052, 10.1158/0008-5472.CAN-16-1708
Speck, 2018, Targeted BiTE expression by an oncolytic vector augments therapeutic efficacy against solid tumors, Clin. Cancer Res., 24, 2128, 10.1158/1078-0432.CCR-17-2651
Yu, 2017, A T-cell engager-armed oncolytic vaccinia virus to target the tumor stroma, Cancer Transl. Med., 3, 122, 10.4103/ctm.ctm_13_17
Chan, 2018, A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma, Cancer Immunol. Res., 6, 776, 10.1158/2326-6066.CIR-17-0649
Ravirala, 2021, Co-delivery of novel bispecific and trispecific engagers by an amplicon vector augments the therapeutic effect of an HSV-based oncolytic virotherapy, J. Immunother. Cancer, 9, 10.1136/jitc-2021-002454
Reale, 2021, Giving oncolytic viruses a free ride: carrier cells for oncolytic virotherapy, Pharmaceutics, 13, 2192, 10.3390/pharmaceutics13122192
Jung, 2017, Oncolytic adenovirus expressing relaxin (YDC002) enhances therapeutic efficacy of gemcitabine against pancreatic cancer, Cancer Lett., 396, 155, 10.1016/j.canlet.2017.03.009
Sette, 2019, GBM-targeted oHSV armed with matrix metalloproteinase 9 enhances anti-tumor activity and animal survival, Mol. Ther. Oncolytics, 15, 214, 10.1016/j.omto.2019.10.005
Xu, 2018, An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma, Nat. Biotechnol., 37, 45, 10.1038/nbt.4302
Gujar, 2018, Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies, Trends Immunol., 39, 209, 10.1016/j.it.2017.11.006
Alvarez-Breckenridge, 2012, NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors, Nat. Med., 18, 1827, 10.1038/nm.3013
Alvarez-Breckenridge, 2012, The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5/T-BET signaling and generation of gamma interferon, J. Virol., 86, 4566, 10.1128/JVI.05545-11
Han, 2015, TGFβ treatment enhances glioblastoma virotherapy by inhibiting the innate immune response, Cancer Res., 75, 5273, 10.1158/0008-5472.CAN-15-0894
Harrington, 2015, Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy, Expert. Rev. Anticancer. Ther., 15, 1389, 10.1586/14737140.2015.1115725
De Lucia, 2020, Retargeted and multi-cytokine-armed herpes virus is a potent cancer endovaccine for local and systemic anti-tumor treatment, Mol. Ther. Oncolytics, 19, 253, 10.1016/j.omto.2020.10.006
Fulci, 2006, Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses, Proc. Natl. Acad. Sci. U. S. A., 103, 12873, 10.1073/pnas.0605496103
Lamfers, 2006, Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging, Mol. Ther., 14, 779, 10.1016/j.ymthe.2006.08.008
Jung, 2017, A hydrogel matrix prolongs persistence and promotes specific localization of an oncolytic adenovirus in a tumor by restricting nonspecific shedding and an antiviral immune response, Biomaterials, 147, 26, 10.1016/j.biomaterials.2017.09.009
Groeneveldt, 2020, Immunotherapeutic potential of TGF-β inhibition and oncolytic viruses, Trends Immunol., 41, 406, 10.1016/j.it.2020.03.003
Hingorani, 2010, The biology of the sodium iodide symporter and its potential for targeted gene delivery, Curr. Cancer Drug Targets, 10, 242, 10.2174/156800910791054194
Lau, 2015, DNA tumor virus oncogenes antagonize the cGAS–STING DNA-sensing pathway, Science, 350, 568, 10.1126/science.aab3291
Gállego Pérez-Larraya, 2022, Oncolytic DNX-2401 virus for pediatric Diffuse Intrinsic Pontine Glioma, New Engl. J. Med., 386, 2471, 10.1056/NEJMoa2202028
Ikeda, 1999, Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses, Nat. Med., 5, 881, 10.1038/11320
Qiao, 2008, Cyclophosphamide facilitates antitumor efficacy against subcutaneous tumors following intravenous delivery of reovirus, Clin. Cancer Res., 14, 259, 10.1158/1078-0432.CCR-07-1510
Cerullo, 2011, Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus, Mol. Ther., 19, 1737, 10.1038/mt.2011.113
Prestwich, 2008, Oncolytic viruses: a novel form of immunotherapy, Expert. Rev. Anticancer. Ther., 8, 1581, 10.1586/14737140.8.10.1581
Saha, 2020, Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma, J. Immunother. Cancer, 8, 10.1136/jitc-2019-000345
Ghonime, 2018, Combination therapy using ruxolitinib and oncolytic HSV renders resistant MPNSTs susceptible to virotherapy, Cancer Immunol. Res., 6, 1499, 10.1158/2326-6066.CIR-18-0014
Ishikawa, 2009, STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity, Nature, 461, 788, 10.1038/nature08476
Barrueto, 2020, Resistance to checkpoint inhibition in cancer immunotherapy, Transl. Oncol., 13, 10.1016/j.tranon.2019.12.010
Puzanov, 2016, Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB–IV melanoma, J. Clin. Oncol., 34, 2619, 10.1200/JCO.2016.67.1529
Chesney, 2018, Randomized, open-label Phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma, J. Clin. Oncol., 36, 1658, 10.1200/JCO.2017.73.7379
Tähtinen, 2015, Adenovirus improves the efficacy of adoptive T-cell therapy by recruiting immune cells to and promoting their activity at the tumor, Cancer Immunol. Res., 3, 915, 10.1158/2326-6066.CIR-14-0220-T
Eckert, 2020, Generation of a tumor-specific chemokine gradient using oncolytic vesicular stomatitis virus encoding CXCL9, Mol. Ther. Oncolytics, 16, 63, 10.1016/j.omto.2019.12.003
Li, 2011, Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer, Mol. Ther., 19, 650, 10.1038/mt.2010.312
Bridle, 2013, Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves primary CD8+ T-cell responses to anticancer vaccines, Oncoimmunology, 2, 10.4161/onci.26013
Pol, 2014, Maraba virus as a potent oncolytic vaccine vector, Mol. Ther., 22, 420, 10.1038/mt.2013.249
Havunen, 2017, Oncolytic adenoviruses armed with tumor necrosis factor alpha and interleukin-2 enable successful adoptive cell therapy, Mol. Ther. Oncolytics, 4, 77, 10.1016/j.omto.2016.12.004
Cervera-Carrascon, 2020, Comparison of clinically relevant oncolytic virus platforms for enhancing T cell therapy of solid tumors, Mol. Ther. Oncolytics, 17, 47, 10.1016/j.omto.2020.03.003
Park, 2020, Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors, Sci. Transl. Med., 12, 10.1126/scitranslmed.aaz1863
Evgin, 2022, Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice, Sci. Transl. Med., 14, 10.1126/scitranslmed.abn2231
Liu, 2020, Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors, N. Engl. J. Med., 382, 545, 10.1056/NEJMoa1910607
Ran, 2022, Natural killer cell homing and trafficking in tissues and tumors: from biology to application, Signal Transduct. Target Ther., 7, 205, 10.1038/s41392-022-01058-z
Hodgins, 2019, Killers 2.0: NK cell therapies at the forefront of cancer control, J. Clin. Invest., 129, 3499, 10.1172/JCI129338
Zhang, 2020, Gasdermin E suppresses tumour growth by activating anti-tumour immunity, Nature, 579, 415, 10.1038/s41586-020-2071-9
Tang, 2018, First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia, Am. J. Cancer Res., 8, 1083
Liu, 2020, Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors, N. Engl. J. Med., 382, 545, 10.1056/NEJMoa1910607
Chen, 2016, A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases, Oncotarget, 7, 27764, 10.18632/oncotarget.8526
Twumasi-Boateng, 2018, Oncolytic viruses as engineering platforms for combination immunotherapy, Nat. Rev. Cancer, 18, 419, 10.1038/s41568-018-0009-4
Chiocca, 2004, A Phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting, Mol. Ther., 10, 958, 10.1016/j.ymthe.2004.07.021
Nakashima, 2014, Modification of HSV-1 to an oncolytic virus, Methods Mol. Biol., 1144, 117, 10.1007/978-1-4939-0428-0_8
Friedman, 2021, Oncolytic HSV-1 G207 immunovirotherapy for pediatric high-grade gliomas, New Engl. J. Med., 384, 1613, 10.1056/NEJMoa2024947
Fu, 2006, Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus, Clin. Cancer Res., 12, 3152, 10.1158/1078-0432.CCR-06-0045
Jochems, 2014, A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates, Cancer Immunol. Immunother., 63, 407, 10.1007/s00262-014-1524-0
Pisklakova, 2016, M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma, Neuro-Oncology, 18, 1088, 10.1093/neuonc/now006
Nounamo, 2017, Myxoma virus optimizes cisplatin for the treatment of ovarian cancer in vitro and in a syngeneic murine dissemination model, Mol. Ther. Oncolytics, 6, 90, 10.1016/j.omto.2017.08.002
Villa, 2016, Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells, Cytotherapy, 18, 465, 10.1016/j.jcyt.2015.12.007
Galanis, 2015, Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer, Cancer Res., 75, 22, 10.1158/0008-5472.CAN-14-2533
Dispenzieri, 2017, Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma, Leukemia, 31, 2791, 10.1038/leu.2017.120
Andtbacka, 2016, Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial, Ann. Surg. Oncol., 23, 4169, 10.1245/s10434-016-5286-0
Otani, 2020, Oncolytic HSV-infected glioma cells activate NOTCH in adjacent tumor cells sensitizing tumors to gamma secretase inhibition, Clin. Cancer Res., 26, 2381, 10.1158/1078-0432.CCR-19-3420
Han, 2015, TGFβ treatment enhances glioblastoma virotherapy by inhibiting the innate immune response, Cancer Res., 75, 5273, 10.1158/0008-5472.CAN-15-0894
Breitbach, 2011, Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans, Nature, 477, 99, 10.1038/nature10358
Möller, 2003, Expression and function of chemokine receptors in human multiple myeloma, Leukemia, 17, 203, 10.1038/sj.leu.2402717
Muthana, 2013, Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis after chemotherapy or irradiation, Cancer Res., 73, 490, 10.1158/0008-5472.CAN-12-3056
Studeny, 2004, Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents, J. Natl. Cancer Inst., 96, 1593, 10.1093/jnci/djh299
Aboody, 2000, Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas, Proc. Natl. Acad. Sci., 97, 12846, 10.1073/pnas.97.23.12846
Ahmed, 2013, A preclinical evaluation of neural stem cell-based cell carrier for targeted antiglioma oncolytic virotherapy, J. Natl. Cancer Inst., 105, 968, 10.1093/jnci/djt141
Nakashima, 2014, Switching a replication-defective adenoviral vector into a replication-competent, oncolytic adenovirus, J. Virol., 88, 345, 10.1128/JVI.02668-13
Sugawara, 2020, Efficacy of a third-generation oncolytic herpes virus G47Δ in advanced stage models of human gastric cancer, Mol. Ther. Oncolytics, 17, 205, 10.1016/j.omto.2020.03.022
Phuong, 2003, Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme, Cancer Res., 63, 2462
Ma, 2021, An oncolytic virus expressing IL-15/IL-15Rα combined with off-the-shelf EGFR-CAR NK cells targets glioblastoma, Cancer Res., 81, 3635, 10.1158/0008-5472.CAN-21-0035
Jonker, 2017, Phase I study of oncolytic virus (OV) MG1 maraba/MAGE-A3 (MG1MA3), with and without transgenic MAGE-A3 adenovirus vaccine (AdMA3) in incurable advanced/metastatic MAGE-A3-expressing solid tumours: CCTG IND. 214, J. Clin. Oncol., 35, 10.1200/JCO.2017.35.15_suppl.e14637
Dey, 2016, Intranasal oncolytic virotherapy with CXCR4-enhanced stem cells extends survival in mouse model of glioma, Stem Cell Rep., 7, 471, 10.1016/j.stemcr.2016.07.024
Simpson, 2012, Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer, Br. J. Cancer, 106, 496, 10.1038/bjc.2011.577
Low, 2015, A randomized, controlled trial of an aerosolized vaccine against measles, N. Engl. J. Med., 372, 1519, 10.1056/NEJMoa1407417
Agarkhedkar, 2014, Safety and immunogenicity of dry powder measles vaccine administered by inhalation: a randomized controlled Phase I clinical trial, Vaccine, 32, 6791, 10.1016/j.vaccine.2014.09.071