744. Heterologous Prime-Boost Schedules of Replication-Defective Adenovirus Serotype 26 and Modified Vaccinia Virus Ankara Vector Vaccines Expressing Ebola Virus Glycoprotein Are Immunogenic and Well Tolerated in Healthy Adults
Session: Oral Abstract Session: Vaccines: New and Established
Friday, October 9, 2015: 10:30 AM
Room: 5--AB
Background:

We report the preliminary data from the first-in-human safety and immunogenicity assessment of a candidate Ebola vaccine strategy incorporating a monovalent Adenovirus-type 26 vector vaccine and a multivalent Modified Vaccinia Ankara vector.

Methods:

We conducted a phase 1, randomized, placebo-controlled, observer-blind trial assessing replication-defective Ad26.ZEBOV (dose 5x1010 vp) and MVA-BN-Filo (dose 1x108 TCID50) given in heterologous prime-boost vaccination schedules to 87 healthy adults in the UK. The interim analysis of safety and immunogenicity in 36 individuals is presented. Participants were randomly allocated in a 1:1 ratio to receive prime Ad26.ZEBOV/boost MVA-BN-Filo or prime MVA-BN-Filo/boost Ad26.ZEBOV at an interval of 4 weeks and further randomized in a 5:1 ratio to study vaccines or placebo. 

Results:

28 days following primary immunization, Ebola glycoprotein (GP) specific IgG responses were seen in 33.3% (95% C.I. 11.8 – 61.6) of MVA-BN-Filo recipients and 93.3% (68 – 99.8) of Ad26.ZEBOV recipients. 21 days post booster dose, Ebola GP IgG was detectable in all vaccine recipients, with geometric mean IgG levels of 10573 ELISA unit/mL (95% C.I. 6452 ­– 17327) in MVA-BN-Filo/Ad26.ZEBOV recipients compared to 4274 ELISA units/mL (95% C.I. 2350 – 7775) in Ad26.ZEBOV/MVA-BN-Filo recipients. Ebola-specific ELISpot T cell responses were highest at 7 days post boost, with 93.3% (68 – 99.8) of MVA-BN-Filo/Ad26.ZEBOV recipients and 86.7% (59.5 – 98.3) of Ad26.ZEBOV/MVA-BN-Filo recipients responding to vaccination. Fever occurred in only 2 vaccine recipients, both following an Ad26.ZEBOV booster. Following prime or boost MVA-BN-Filo immunization, transient local and systemic reactions were observed in 17/30 (56.7%) and 11/30 (36.7%) of participants respectively, compared with 27/30 (90%) for both local and systemic reactions following Ad26.ZEBOV.

Conclusion:

The use of these vaccines in either schedule was well-tolerated by healthy adult volunteers with induction of humoral and cellular immunity in the vast majority of vaccinees. This represents a promising new immunization strategy against Ebola. Phase 3 efficacy studies are planned to begin later this year in West Africa.

Iain Milligan, MRCP1, Malick Gibani, MRCP1, Danielle Campbell, BScN, DTN1, Elizabeth Clutterbuck, PhD1, Richard Sewell, BA1, Emma Plested, -1, Elizabeth Nuthall, BSc1, Merryn Voysey, MBiostat2, Nicola Orzabal De La Quintana, BSc3, Georgi Shukarev, MD3, Carla Truyers, PhD3, Wilbert Van Duijnhoven, MSc3, Kerstin Luhn, PhD3, Macaya Douoguih, MD, MPH3, Katie Ewer, BSc (Hons), PhD4, Adrian V.S. Hill, DM, DPhil4, Brian Angus, MD, FRCP5, Andrew J Pollard, FRCPCH, PhD1 and Matthew Snape, MD1, (1)Oxford Vaccine Group, University of Oxford, Oxford, United Kingdom, (2)Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom, (3)Janssen, Pharmaceutical Companies of Johnson & Johnson, Leiden, Netherlands, (4)Jenner Institute, University of Oxford, Oxford, United Kingdom, (5)Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

Disclosures:

I. Milligan, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research grant and Research support

M. Gibani, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research grant and Research support

D. Campbell, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

E. Clutterbuck, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research grant and Research support

R. Sewell, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

E. Plested, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

E. Nuthall, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

M. Voysey, None

N. Orzabal De La Quintana, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

G. Shukarev, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

C. Truyers, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

W. Van Duijnhoven, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

K. Luhn, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

M. Douoguih, Janssen, Pharmaceutical Companies of Johnson & Johnson: Employee , Salary

K. Ewer, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research grant

A. V. S. Hill, Coinventor of patented heterologous prime boost vaccination schedules: Coinventor , Intellectual property

B. Angus, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

A. J. Pollard, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research grant and Research support

M. Snape, Janssen, Pharmaceutical Companies of Johnson & Johnson: Investigator , Research support

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