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Heterologous two-dose vaccination with simian adenovirus and poxvirus vectors elicits long-lasting cellular immunity to influenza virus A in healthy adults

Heterologous two-dose vaccination with simian adenovirus and poxvirus vectors elicits long-lasting cellular immunity to influenza virus A in healthy adults
Heterologous two-dose vaccination with simian adenovirus and poxvirus vectors elicits long-lasting cellular immunity to influenza virus A in healthy adults
Background:

T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults.

Methods:

We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months.

Findings:

Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1.

Interpretation:

A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A.

Funding Source:

Medical Research Council UK, NIHR BMRC Oxford.
146–154
Coughlan, L.
894d2b90-1903-43cb-b2fd-490c7dd810ac
Sridhar, S.
aa953d9f-5ab8-4419-8a03-83513d230218
Payne, R.
47b52694-90b6-499c-aea6-784a497ac132
Edmans, M.
c0b5c4ac-224a-409d-9e1a-1e7b15257692
Milicic, A.
cb4043ee-d297-4dc5-a8ee-5837dc244b12
Venkatraman, N.
404c9a0a-354c-43aa-ac4e-c08e398655e0
Lugonja, B.
cb83bff8-3a91-4006-bb9a-5ca5f731e360
Clifton, L.
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Qi, C.
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Folegatti, P.M
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Roberts, R.
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Lawrie, A.M
d7d414ee-b481-4644-bcf7-b5ef566dc993
De Graaf, H.
447e78ed-346f-45bb-9238-fce2118d5559
Sukhtankar, P.
b1774b6f-c957-4385-87aa-14ac647983b5
Faust, S.N.
f97df780-9f9b-418e-b349-7adf63e150c1
Lewis, D.J.M
d1493237-0a32-4633-97c2-b099447cc978
Lambe, T.
8460588d-e4ab-4503-abda-5e9f750be64a
Hill, A.V.S.
d87e812b-1fe6-4afb-a960-187bd3103c7e
Gilbert, S.C.
458027c0-e56d-4eab-b4c8-7ce1f259e48f
Coughlan, L.
894d2b90-1903-43cb-b2fd-490c7dd810ac
Sridhar, S.
aa953d9f-5ab8-4419-8a03-83513d230218
Payne, R.
47b52694-90b6-499c-aea6-784a497ac132
Edmans, M.
c0b5c4ac-224a-409d-9e1a-1e7b15257692
Milicic, A.
cb4043ee-d297-4dc5-a8ee-5837dc244b12
Venkatraman, N.
404c9a0a-354c-43aa-ac4e-c08e398655e0
Lugonja, B.
cb83bff8-3a91-4006-bb9a-5ca5f731e360
Clifton, L.
f6896771-a062-46b3-85a7-bdb1639a2ab0
Qi, C.
bf60b9f9-854c-4c33-ab1b-08985fb15a3f
Folegatti, P.M
3c030f4b-b96f-4c0d-bffd-c6caebb00ac3
Roberts, R.
264b15eb-2178-4342-aa07-630107ce2299
Lawrie, A.M
d7d414ee-b481-4644-bcf7-b5ef566dc993
De Graaf, H.
447e78ed-346f-45bb-9238-fce2118d5559
Sukhtankar, P.
b1774b6f-c957-4385-87aa-14ac647983b5
Faust, S.N.
f97df780-9f9b-418e-b349-7adf63e150c1
Lewis, D.J.M
d1493237-0a32-4633-97c2-b099447cc978
Lambe, T.
8460588d-e4ab-4503-abda-5e9f750be64a
Hill, A.V.S.
d87e812b-1fe6-4afb-a960-187bd3103c7e
Gilbert, S.C.
458027c0-e56d-4eab-b4c8-7ce1f259e48f

Coughlan, L., Sridhar, S., Payne, R., Edmans, M., Milicic, A., Venkatraman, N., Lugonja, B., Clifton, L., Qi, C., Folegatti, P.M, Roberts, R., Lawrie, A.M, De Graaf, H., Sukhtankar, P., Faust, S.N., Lewis, D.J.M, Lambe, T., Hill, A.V.S. and Gilbert, S.C. (2018) Heterologous two-dose vaccination with simian adenovirus and poxvirus vectors elicits long-lasting cellular immunity to influenza virus A in healthy adults. EBioMedicine, 29, 146–154. (doi:10.1016/j.ebiom.2018.02.011).

Record type: Article

Abstract

Background:

T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults.

Methods:

We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months.

Findings:

Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1.

Interpretation:

A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A.

Funding Source:

Medical Research Council UK, NIHR BMRC Oxford.

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More information

Accepted/In Press date: 13 February 2018
e-pub ahead of print date: 15 February 2018
Published date: March 2018

Identifiers

Local EPrints ID: 418728
URI: http://eprints.soton.ac.uk/id/eprint/418728
PURE UUID: 8c74e187-a8a1-4445-8f1f-272856c1e278
ORCID for S.N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 20 Mar 2018 17:30
Last modified: 26 Nov 2021 02:50

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Contributors

Author: L. Coughlan
Author: S. Sridhar
Author: R. Payne
Author: M. Edmans
Author: A. Milicic
Author: N. Venkatraman
Author: B. Lugonja
Author: L. Clifton
Author: C. Qi
Author: P.M Folegatti
Author: R. Roberts
Author: A.M Lawrie
Author: H. De Graaf
Author: P. Sukhtankar
Author: S.N. Faust ORCID iD
Author: D.J.M Lewis
Author: T. Lambe
Author: A.V.S. Hill
Author: S.C. Gilbert

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