MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines

被引:288
作者
Khurana, Surender [1 ]
Verma, Nitin [1 ]
Yewdell, Jonathan W. [2 ]
Hilbert, Anne Katrin [3 ]
Castellino, Flora [4 ]
Lattanzi, Maria [4 ]
Del Giudice, Giuseppe [4 ]
Rappuoli, Rino [4 ]
Golding, Hana [1 ]
机构
[1] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA
[2] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA
[3] Novartis Vaccines & Diagnost GmbH, D-35041 Marburg, Germany
[4] Novartis Vaccines & Diagnost Res Ctr, I-53100 Siena, Italy
关键词
A H1N1 VACCINE; CELL RESPONSE; H5N1; VACCINE; VIRUS; IMMUNOGENICITY; MATURATION; SAFETY; NEUTRALIZATION; ANTIGEN; RECOGNITION;
D O I
10.1126/scitranslmed.3002336
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Oil-in-water adjuvants have been shown to improve immune responses against pandemic influenza vaccines as well as reduce the effective vaccine dose, increasing the number of doses available to meet global vaccine demand. Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity, diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. In adults and children, MF59 selectively enhanced antibody responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire. Antibody affinity, as inferred by greatly diminished (>= 10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. Moreover, MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. For both pandemic influenza vaccines, there was a close correlation between serum antibody affinity and virus-neutralizing capacity. Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines.
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页数:9
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共 47 条
[1]   Pseudoparticle neutralization is a reliable assay to measure immunity and cross-reactivity to H5N1 influenza viruses [J].
Alberini, Isabella ;
Del Tordello, Elena ;
Fasolo, Alba ;
Temperton, Nigel J. ;
Galli, Grazia ;
Gentile, Chiara ;
Montomoli, Emanuele ;
Hilbert, Anne K. ;
Banzhoff, Angelika ;
Del Giudice, Giuseppe ;
Donnelly, John J. ;
Rappuoli, Rino ;
Capecchi, Barbara .
VACCINE, 2009, 27 (43) :5998-6003
[2]   Neutralizing antiviral B cell responses [J].
Bachmann, MF ;
Zinkernagel, RM .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :235-270
[3]   The role of antibody concentration and avidity in antiviral protection [J].
Bachmann, MF ;
Kalinke, U ;
Althage, A ;
Freer, G ;
Burkhart, C ;
Roost, HP ;
Aguet, M ;
Hengartner, H ;
Zinkernagel, RM .
SCIENCE, 1997, 276 (5321) :2024-2027
[4]   Affinity dependence of the B cell response to antigen: A threshold, a ceiling, and the importance of off-rate [J].
Batista, FD ;
Neuberger, MS .
IMMUNITY, 1998, 8 (06) :751-759
[5]   Safety and Immunogenicity of Multiple and Higher Doses of an Inactivated Influenza A/H5N1 Vaccine [J].
Beigel, John H. ;
Voell, Jocelyn ;
Huang, Chiung-yu ;
Burbelo, Peter D. ;
Lane, H. Clifford .
JOURNAL OF INFECTIOUS DISEASES, 2009, 200 (04) :501-509
[6]   Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults [J].
Bernstein, David I. ;
Edwards, Kathryn M. ;
Dekker, Cornelia L. ;
Belshe, Robert ;
Talbot, Helen K. B. ;
Graham, Irene L. ;
Noah, Diana L. ;
He, Fenhua ;
Hill, Heather .
JOURNAL OF INFECTIOUS DISEASES, 2008, 197 (05) :667-675
[7]   Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6-35 months [J].
Carmona, Alfonso ;
Omenaca, Felix ;
Tejedor, Juan C. ;
Merino, Jose M. ;
Vaman, Tejaswini ;
Dieussaert, Ilse ;
Gillard, Paul ;
Aristegui, Javier .
VACCINE, 2010, 28 (36) :5837-5844
[8]   Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes [J].
Clara Monsalvo, Ana ;
Batalle, Juan P. ;
Florencia Lopez, M. ;
Krause, Jens C. ;
Klemenc, Jennifer ;
Zea Hernandez, Johanna ;
Maskin, Bernardo ;
Bugna, Jimena ;
Rubinstein, Carlos ;
Aguilar, Leandro ;
Dalurzo, Liliana ;
Libster, Romina ;
Savy, Vilma ;
Baumeister, Elsa ;
Aguilar, Liliana ;
Cabral, Graciela ;
Font, Julia ;
Solari, Liliana ;
Weller, Kevin P. ;
Johnson, Joyce ;
Echavarria, Marcela ;
Edwards, Kathryn M. ;
Chappell, James D. ;
Crowe, James E., Jr. ;
Williams, John V. ;
Melendi, Guillermina A. ;
Polack, Fernando P. .
NATURE MEDICINE, 2011, 17 (02) :195-U225
[9]   Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine. [J].
Clark, Tristan W. ;
Pareek, Manish ;
Hoschler, Katja ;
Dillon, Helen ;
Nicholson, Karl G. ;
Groth, Nicola ;
Stephenson, Iain .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (25) :2424-2435
[10]   Vaccine Adjuvants: Putting Innate Immunity to Work [J].
Coffman, Robert L. ;
Sher, Alan ;
Seder, Robert A. .
IMMUNITY, 2010, 33 (04) :492-503