Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia Ankara vaccine regimens in humans

Simian adenoviral and modified vaccinia Ankara (MVA) viral vectors used in heterologous prime-boost strategies are potent inducers of T cells against encoded antigens and are in advanced testing as vaccine carriers for a wide range of infectious agents and cancers. It is unclear if these responses c...

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Veröffentlicht in:npj vaccines 2020-10, Vol.5 (1), p.94-94, Article 94
Hauptverfasser: Capone, Stefania, Brown, Anthony, Hartnell, Felicity, Sorbo, Mariarosaria Del, Traboni, Cinzia, Vassilev, Ventzislav, Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, Folgori, Antonella, Klenerman, Paul, Barnes, Eleanor, Swadling, Leo
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container_issue 1
container_start_page 94
container_title npj vaccines
container_volume 5
creator Capone, Stefania
Brown, Anthony
Hartnell, Felicity
Sorbo, Mariarosaria Del
Traboni, Cinzia
Vassilev, Ventzislav
Colloca, Stefano
Nicosia, Alfredo
Cortese, Riccardo
Folgori, Antonella
Klenerman, Paul
Barnes, Eleanor
Swadling, Leo
description Simian adenoviral and modified vaccinia Ankara (MVA) viral vectors used in heterologous prime-boost strategies are potent inducers of T cells against encoded antigens and are in advanced testing as vaccine carriers for a wide range of infectious agents and cancers. It is unclear if these responses can be further enhanced or sustained with reboosting strategies. Furthermore, despite the challenges involved in MVA manufacture dose de-escalation has not been performed in humans. In this study, healthy volunteers received chimpanzee-derived adenovirus-3 and MVA vaccines encoding the non-structural region of hepatitis C virus (ChAd3-NSmut/MVA-NSmut) 8 weeks apart. Volunteers were then reboosted with a second round of ChAd3-NSmut/MVA-NSmut or MVA-NSmut vaccines 8 weeks or 1-year later. We also determined the capacity of reduced doses of MVA-NSmut to boost ChAd3-NSmut primed T cells. Reboosting was safe, with no enhanced reactogenicity. Reboosting after an 8-week interval led to minimal re-expansion of transgene-specific T cells. However, after a longer interval, T cell responses expanded efficiently and memory responses were enhanced. The 8-week interval regimen induced a higher percentage of terminally differentiated and effector memory T cells. Reboosting with MVA-NSmut alone was as effective as with ChAd3-NSmut/MVA-NSmut. A ten-fold lower dose of MVA (2 × 10 7 pfu) induced high-magnitude, sustained, broad, and functional Hepatitis C virus (HCV)-specific T cell responses, equivalent to standard doses (2 × 10 8  pfu). Overall, we show that following Ad/MVA prime-boost vaccination reboosting is most effective after a prolonged interval and is productive with MVA alone. Importantly, we also show that a ten-fold lower dose of MVA is as potent in humans as the standard dose.
doi_str_mv 10.1038/s41541-020-00240-0
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subjects 631/250/2152
631/250/590
631/250/590/1867
Biomedical and Life Sciences
Biomedicine
Infectious Diseases
Medical Microbiology
Public Health
Vaccine
Virology
title Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia Ankara vaccine regimens in humans
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