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MF59™ as a vaccine adjuvant: a review of safety and immunogenicity

Pages 1135-1141 | Published online: 09 Jan 2014

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Ozan S. Kumru, Sakshi Bajoria, Kawaljit Kaur, John M. Hickey, Greta Van Slyke, Jennifer Doering, Katherine Berman, Charles Richardson, Hans Lien, Harry Kleanthous, Nicholas J. Mantis, Sangeeta B. Joshi & David B. Volkin. (2023) Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD). Human Vaccines & Immunotherapeutics 19:2.
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Alex C. D. Salyer & Sunil A. David. (2018) Transcriptomal signatures of vaccine adjuvants and accessory immunostimulation of sentinel cells by toll-like receptor 2/6 agonists. Human Vaccines & Immunotherapeutics 14:7, pages 1686-1696.
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Walthère Dewé, Christelle Durand, Sandie Marion, Lidia Oostvogels, Jeanne-Marie Devaster & Marc Fourneau. (2016) A multi-criteria decision making approach to identify a vaccine formulation. Journal of Biopharmaceutical Statistics 26:2, pages 352-364.
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Yumei Wen & Yan Shi. (2016) Alum: an old dog with new tricks. Emerging Microbes & Infections 5:1, pages 1-5.
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Barbara Camilloni, Michela Basileo, Stefano Valente, Emilia Nunzi & Anna Maria Iorio. (2015) Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review. Human Vaccines & Immunotherapeutics 11:3, pages 553-563.
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Markus Knuf, Geert Leroux-Roels, Hans Rümke, Luis Rivera, Paola Pedotti, Ashwani Kumar Arora, Maria Lattanzi, Dorothee Kieninger & Giovanni Della Cioppa. (2015) Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children . Human Vaccines & Immunotherapeutics 11:2, pages 358-376.
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Orli Even-Or, Sarit Samira, Ronald Ellis, Eli Kedar & Yechezkel Barenholz. (2013) Adjuvanted influenza vaccines. Expert Review of Vaccines 12:9, pages 1095-1108.
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Christopher B Fox & Jean Haensler. (2013) An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants. Expert Review of Vaccines 12:7, pages 747-758.
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Jesse Bodle, Kirsten Vandenberg, Karen Laurie, Ian G. Barr, Ying Zhang & Steven Rockman. (2023) An ELISA-based assay for determining haemagglutinin potency in egg, cell, or recombinant protein derived influenza vaccines. Frontiers in Immunology 14.
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Rokon Uz Zaman, Rikhav P. Gala, Amit Bansal, Priyal Bagwe & Martin J. D'Souza. (2022) Preclinical evaluation of a microparticle-based transdermal vaccine patch against metastatic breast cancer. International Journal of Pharmaceutics 627, pages 122249.
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Geoffrey J. Gorse, Stephen Grimes, Helen Buck, Hussain Mulla, Peter White, Heather Hill, Jeanine May, Sharon E. Frey & Peter Blackburn. (2022) MAS-1, a novel water-in-oil adjuvant/delivery system, with reduced seasonal influenza vaccine hemagglutinin dose may enhance potency, durability and cross-reactivity of antibody responses in the elderly. Vaccine 40:10, pages 1472-1482.
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Geoffrey J. Gorse, Stephen Grimes, Helen Buck, Hussain Mulla, Peter White, Heather Hill, Jeanine May, Sharon E. Frey & Peter Blackburn. (2022) A phase 1 dose-sparing, randomized clinical trial of seasonal trivalent inactivated influenza vaccine combined with MAS-1, a novel water-in-oil adjuvant/delivery system. Vaccine 40:9, pages 1271-1281.
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Myriam Lamrayah, Capucine Phelip, Céline Coiffier, Céline Lacroix, Thibaut Willemin, Thomas Trimaille & Bernard Verrier. (2022) A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response. Pharmaceutics 14:1, pages 107.
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Farrhana Ziana Firdaus, Mariusz Skwarczynski & Istvan Toth. 2022. Vaccine Design. Vaccine Design 145 178 .
Naorem Nihesh, Saikat Manna, Bradley Studnitzer, Jingjing Shen & Aaron P. Esser-Kahn. (2021) A synthetic pathogen mimetic molecule induces a highly amplified synergistic immune response via activation of multiple signaling pathways . Chemical Science 12:19, pages 6646-6651.
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Reza Keikha, Karim Daliri & Ali Jebali. (2021) The Use of Nanobiotechnology in Immunology and Vaccination. Vaccines 9:2, pages 74.
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Daniel Watterson, Danushka K Wijesundara, Naphak Modhiran, Francesca L Mordant, Zheyi Li, Michael S Avumegah, Christopher LD McMillan, Julia Lackenby, Kate Guilfoyle, Geert van Amerongen, Koert Stittelaar, Stacey TM Cheung, Summa Bibby, Mallory Daleris, Kym Hoger, Marianne Gillard, Eve Radunz, Martina L Jones, Karen Hughes, Ben Hughes, Justin Goh, David Edwards, Judith Scoble, Lesley Pearce, Lukasz Kowalczyk, Tram Phan, Mylinh La, Louis Lu, Tam Pham, Qi Zhou, David A Brockman, Sherry J Morgan, Cora Lau, Mai H Tran, Peter Tapley, Fernando Villalón‐Letelier, James Barnes, Andrew Young, Noushin Jaberolansar, Connor AP Scott, Ariel Isaacs, Alberto A Amarilla, Alexander A Khromykh, Judith MA van den Brand, Patrick C Reading, Charani Ranasinghe, Kanta Subbarao, Trent P Munro, Paul R Young & Keith J Chappell. (2021) Preclinical development of a molecular clamp‐stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2. Clinical & Translational Immunology 10:4.
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Marta Sisteré-Oró, Gabriel K. Pedersen, Lorena Córdoba, Sergi López-Serrano, Dennis Christensen & Ayub Darji. (2020) Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate. Veterinary Research 51:1.
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Tahoora Mousavi, Sogol Sattari Saravi, Reza Valadan, Mohammad Reza Haghshenas, Alireza Rafiei, Hamed Jafarpour & Amir Shamshirian. (2019) Different types of adjuvants in prophylactic and therapeutic human papillomavirus vaccines in laboratory animals: a systematic review. Archives of Virology 165:2, pages 263-284.
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Thomas Trimaille, Céline Lacroix & Bernard Verrier. (2019) Self-assembled amphiphilic copolymers as dual delivery system for immunotherapy. European Journal of Pharmaceutics and Biopharmaceutics 142, pages 232-239.
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Aline F. Teixeira, Luis G.V. Fernandes, Maria F. Cavenague, Maria B. Takahashi, Jademilson C. Santos, Felipe J. Passalia, Brenda B. Daroz, Leandro T. Kochi, Monica L. Vieira & Ana L.T.O. Nascimento. (2019) Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines. Vaccine 37:30, pages 3961-3973.
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Shilpa Ray & Mrutyunjay Suar. 2018. Biomedical Engineering. Biomedical Engineering 1353 1401 .
Michael T. Hensel, Jason D. Marshall, Michael R. Dorwart, Darren S. Heeke, Eileen Rao, Padmaja Tummala, Li Yu, Gary H. Cohen, Roselyn J. Eisenberg & Derek D. Sloan. (2017) Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir. Journal of Virology 91:9.
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T. Barclay & N. Petrovsky. 2017. Micro and Nanotechnology in Vaccine Development. Micro and Nanotechnology in Vaccine Development 127 147 .
Eun-Ju Ko, Young-Tae Lee, Ki-Hye Kim, Yu-Jin Jung, Youri Lee, Timothy L. Denning & Sang-Moo Kang. (2016) Effects of MF59 Adjuvant on Induction of Isotype-Switched IgG Antibodies and Protection after Immunization with T-Dependent Influenza Virus Vaccine in the Absence of CD4 + T Cells . Journal of Virology 90:15, pages 6976-6988.
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Niels Peter H. Knudsen, Anja Olsen, Cecilia Buonsanti, Frank Follmann, Yuan Zhang, Rhea N. Coler, Christopher B. Fox, Andreas Meinke, Ugo D´Oro, Daniele Casini, Alessandra Bonci, Rolf Billeskov, Ennio De Gregorio, Rino Rappuoli, Ali M. Harandi, Peter Andersen & Else Marie Agger. (2016) Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens. Scientific Reports 6:1.
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Takami Akagi & Mitsuru Akashi. 2016. Nanomaterials in Pharmacology. Nanomaterials in Pharmacology 439 455 .
Wenting Xu, Mei Zheng, Feng Zhou & Ze Chen. (2015) Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice. Clinical and Vaccine Immunology 22:3, pages 327-335.
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Shilpa Ray & Mrutyunjay Suar. 2015. Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering. Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering 221 268 .
Young-Tae LeeKi-Hye KimEun-Ju KoYu-Na LeeMin-Chul KimYoung-Man KwonYinghua TangMin-Kyoung ChoYoun-Jeong LeeSang-Moo Kang. (2014) New vaccines against influenza virus. Clinical and Experimental Vaccine Research 3:1, pages 12.
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Hans C Rümke, Jan Hendrik Richardus, Lars Rombo, Karlis Pauksens, Georg Plaßmann, Christelle Durand, Jeanne-Marie Devaster, Walthère Dewé & Lidia Oostvogels. (2013) Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial. BMC Infectious Diseases 13:1.
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Million A. Tegenge & Robert J. Mitkus. (2013) A physiologically-based pharmacokinetic (PBPK) model of squalene-containing adjuvant in human vaccines. Journal of Pharmacokinetics and Pharmacodynamics 40:5, pages 545-556.
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Janet E McElhaney, Jiri Beran, Jeanne-Marie Devaster, Meral Esen, Odile Launay, Geert Leroux-Roels, Guillermo M Ruiz-Palacios, Gerrit A van Essen, Adrian Caplanusi, Carine Claeys, Christelle Durand, Xavier Duval, Mohamed El Idrissi, Ann R Falsey, Gregory Feldman, Sharon E Frey, Florence Galtier, Shinn-Jang Hwang, Bruce L Innis, Martina Kovac, Peter Kremsner, Shelly McNeil, Andrzej Nowakowski, Jan Hendrik Richardus, Andrew Trofa & Lidia Oostvogels. (2013) AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. The Lancet Infectious Diseases 13:6, pages 485-496.
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Iván Bihari, Gyula Pánczél, Jozsef Kovacs, Jenny Beygo & Elena Fragapane. (2012) Assessment of Antigen-Specific and Cross-Reactive Antibody Responses to an MF59-Adjuvanted A/H5N1 Prepandemic Influenza Vaccine in Adult and Elderly Subjects. Clinical and Vaccine Immunology 19:12, pages 1943-1948.
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Terho Heikkinen, James Young, Erik van Beek, Henk Franke, Thomas Verstraeten, John G. Weil & Giovanni Della Cioppa. (2012) Safety of MF59-adjuvanted A/H1N1 influenza vaccine in pregnancy: a comparative cohort study. American Journal of Obstetrics and Gynecology 207:3, pages 177.e1-177.e8.
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William C. Weldon, Vladimir G. Zarnitsyn, E. Stein Esser, Misha T. Taherbhai, Dimitrios G. Koutsonanos, Elena V. Vassilieva, Ioanna Skountzou, Mark R. Prausnitz & Richard W. Compans. (2012) Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine. PLoS ONE 7:7, pages e41501.
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Peter M. Gray, Gail Forrest, Thomas Wisniewski, Gene Porter, Daniel C. Freed, Julie A. DeMartino, Dennis M. Zaller, Zhiqiang Guo, Joseph Leone, Tong-Ming Fu & Kalpit A. Vora. (2012) Evidence for cyclic diguanylate as a vaccine adjuvant with novel immunostimulatory activities. Cellular Immunology 278:1-2, pages 113-119.
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Christoph Hatz, Frank von Sonnenburg, Daniela Casula, Maria Lattanzi & Geert Leroux-Roels. (2012) A randomized clinical trial to identify the optimal antigen and MF59® adjuvant dose of a monovalent A/H1N1 pandemic influenza vaccine in healthy adult and elderly subjects. Vaccine 30:23, pages 3470-3477.
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Qiang Zou, Yanxin Hu, Jia Xue, Xiaoxu Fan, Yi Jin, Xianghua Shi, Di Meng, Xianzheng Wang, Congcong Feng, Xiaoping Xie, Yizhi Zhang, Youmin Kang, Xiaoxuan Liang, Bing Wu, Ming Wang & Bin Wang. (2012) Use of Praziquantel as an Adjuvant Enhances Protection and Tc-17 Responses to Killed H5N1 Virus Vaccine in Mice. PLoS ONE 7:4, pages e34865.
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Mariarosaria Marinaro, Giovanni Rezza, Giuseppe Del Giudice, Valeriana Colao, Elvira Tarsitano, Michele Camero, Michele Losurdo, Canio Buonavoglia & Maria Tempesta. (2012) A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats. PLoS ONE 7:4, pages e34913.
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Antu K. Dey, Brian Burke, Yide Sun, Karin Hartog, Jonathan L. Heeney, David Montefiori, Indresh K. Srivastava & Susan W. Barnett. (2012) Use of a polyanionic carbomer, Carbopol971P, in combination with MF59, improves antibody responses to HIV-1 envelope glycoprotein. Vaccine 30:17, pages 2749-2759.
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Steven G Reed, Christopher B Fox & Darrick CarterJennifer WhitakerNadine RouphaelMark J Mulligan. 2012. Emulsion-based Vaccine Adjuvants. Emulsion-based Vaccine Adjuvants 6 19 .
Kyung-Dong Bae. (2011) The Evolution and Value of Diphtheria Vaccine. KSBB Journal 26:6, pages 491-504.
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Geetanjali Agnihotri, Breanna M. Crall, Tyler C. Lewis, Timothy P. Day, Rajalakshmi Balakrishna, Hemamali J. Warshakoon, Subbalakshmi S. Malladi & Sunil A. David. (2011) Structure–Activity Relationships in Toll-Like Receptor 2-Agonists Leading to Simplified Monoacyl Lipopeptides. Journal of Medicinal Chemistry 54:23, pages 8148-8160.
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Yong Taik Lim, Sang-Mu Shim, Young-Woock Noh, Kyung-Soon Lee, Doo-Yeol Choi, Hiroshi Uyama, Hee Ho Bae, Ji Hyun Kim, Kwan Soo Hong, Moon-Hee Sung & Haryoung Poo. (2011) Bioderived Polyelectrolyte Nanogels for Robust Antigen Loading and Vaccine Adjuvant Effects. Small 7:23, pages 3281-3286.
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David I. Bernstein, Hana M. El. Sahly, Wendy A. Keitel, Mark Wolff, Gina Simone, Claire Segawa, Susan Wong, Daniel Shelly, Neal S. Young & Walla Dempsey. (2011) Safety and immunogenicity of a candidate parvovirus B19 vaccine. Vaccine 29:43, pages 7357-7363.
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Hee Jin Cheong, Joon Young Song, Jung Yeon Heo, Ji Yun Noh, Won Suk Choi, Dae Won Park, Seong-Heon Wie & Woo Joo Kim. (2011) Immunogenicity and Safety of the Influenza A/H1N1 2009 Inactivated Split-Virus Vaccine in Young and Older Adults: MF59-Adjuvanted Vaccine versus Nonadjuvanted Vaccine. Clinical and Vaccine Immunology 18:8, pages 1358-1364.
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J. Li, J. Guo, Z. Su, M. Hu, W. Liu & Q. Wei. (2011) Calcineurin subunit B activates dendritic cells and acts as a cancer vaccine adjuvant. International Immunology 23:5, pages 327-334.
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Wei Wang & Manmohan Singh. (2011) Selection of Adjuvants for Enhanced Vaccine Potency. World Journal of Vaccines 01:02, pages 33-78.
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