Coadministration of Seasonal Influenza Vaccine and MVA-NP+M1 Simultaneously Achieves Potent Humoral and Cell-Mediated Responses

被引:87
作者
Antrobus, Richard D. [1 ]
Berthoud, Tamara K. [1 ]
Mullarkey, Caitlin E. [1 ]
Hoschler, Katja [2 ]
Coughlan, Lynda [1 ]
Zambon, Maria [2 ]
Hill, Adrian V. S. [1 ]
Gilbert, Sarah C. [1 ]
机构
[1] Univ Oxford, Jenner Inst, Oxford, England
[2] Publ Hlth England, Resp Virus Unit, London, England
关键词
T-CELLS; IMMUNOGENICITY; VIRUS; PROTECTION; EFFICACY; TRIAL; SAFETY;
D O I
10.1038/mt.2013.162
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Current seasonal influenza vaccines have reduced immunogenicity and are of suboptimal efficacy in older adults. We have previously shown that the novel candidate vaccine MVA-NP+M1 is able to boost memory T cell responses in adults aged 50-85 years. Preclinical studies have demonstrated that viral vectored vaccines can act as adjuvants when coadministered with protein-based vaccines. We have conducted a phase I clinical trial to compare the coadministration of seasonal influenza vaccine and MVA-NP+M1 with seasonal influenza vaccine alone in adults aged 50 years and above. This combination of vaccines was safe and well tolerated. T cell responses to internal influenza proteins were boosted to significantly higher levels in the group receiving MVA-NP+M1 compared with the group receiving seasonal influenza vaccine alone. Rates of seroprotection and seroconversion against the three vaccine strains were similar in both groups; however, there was a significant increase in the geometric mean titer ratio for the H3N2 component of seasonal influenza vaccine in the coadministration group. While some vaccine combinations result in immune interference, the coadministration of MVA-NP+M1 alongside seasonal influenza vaccine is shown here to increase some influenza strain-specific antibody responses and boost memory T cells capable of recognizing a range of influenza A subtypes.
引用
收藏
页码:233 / 238
页数:6
相关论文
共 32 条
[1]  
[Anonymous], 1997, NOT GUID HARM REQ IN
[2]  
[Anonymous], 2009, INFL SEAS FACT SHEET
[3]   A T Cell-Inducing Influenza Vaccine for the Elderly: Safety and Immunogenicity of MVA-NP+M1 in Adults Aged over 50 Years [J].
Antrobus, Richard D. ;
Lillie, Patrick J. ;
Berthoud, Tamara K. ;
Spencer, Alexandra J. ;
McLaren, James E. ;
Ladell, Kristin ;
Lambe, Teresa ;
Milicic, Anita ;
Price, David A. ;
Hill, Adrian V. S. ;
Gilbert, Sarah C. .
PLOS ONE, 2012, 7 (10)
[4]   Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB) [J].
Bar-On, Edna S. ;
Goldberg, Elad ;
Hellmann, Sarah ;
Leibovici, Leonard .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2012, (04)
[5]   Potent CD8+ T-Cell Immunogenicity in Humans of a Novel Heterosubtypic Influenza A Vaccine, MVA-NP+M1 [J].
Berthoud, Tamara K. ;
Hamill, Matthew ;
Lillie, Patrick J. ;
Hwenda, Lenias ;
Collins, Katharine A. ;
Ewer, Katie J. ;
Milicic, Anita ;
Poyntz, Hazel C. ;
Lambe, Teresa ;
Fletcher, Helen A. ;
Hill, Adrian V. S. ;
Gilbert, Sarah C. .
CLINICAL INFECTIOUS DISEASES, 2011, 52 (01) :1-7
[6]   Antibody and Th1-type cell-mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine [J].
Chen, Wilbur H. ;
Cross, Alan S. ;
Edelman, Robert ;
Sztein, Marcelo B. ;
Blackwelder, William C. ;
Pasetti, Marcela F. .
VACCINE, 2011, 29 (16) :2865-2873
[7]   RETRACTED: Innate Immune Sensing of Modified Vaccinia Virus Ankara (MVA) Is Mediated by TLR2-TLR6, MDA-5 and the NALP3 Inflammasome (Retracted Article) [J].
Delaloye, Julie ;
Roger, Thierry ;
Steiner-Tardivel, Quynh-Giao ;
Le Roy, Didier ;
Reymond, Marlies Knaup ;
Akira, Shizuo ;
Petrilli, Virginie ;
Gomez, Carmen E. ;
Perdiguero, Beatriz ;
Tschopp, Juerg ;
Pantaleo, Giuseppe ;
Esteban, Mariano ;
Calandra, Thierry .
PLOS PATHOGENS, 2009, 5 (06)
[8]   Influenza vaccine immunology [J].
Dormitzer, Philip R. ;
Galli, Grazia ;
Castellino, Flora ;
Golding, Hana ;
Khurana, Surender ;
Del Giudice, Giuseppe ;
Rappuoli, Rino .
IMMUNOLOGICAL REVIEWS, 2011, 239 :167-177
[9]   Molecular analysis of an outbreak of influenza in the United Kingdom [J].
Ellis, JS ;
Zambon, MC .
EUROPEAN JOURNAL OF EPIDEMIOLOGY, 1997, 13 (04) :369-372
[10]   Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older [J].
Falsey, Ann R. ;
Treanor, John J. ;
Tornieporth, Nadia ;
Capellan, Jose ;
Gorse, Geoffrey J. .
JOURNAL OF INFECTIOUS DISEASES, 2009, 200 (02) :172-180