The University of Southampton
University of Southampton Institutional Repository

Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions

Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions
Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions
The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen — a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers. We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been induced by immunization in humans, with levels greatly exceeding the serum antibody responses observed in African adults following years of natural malaria exposure. These data support the progression of RH5-based vaccines to human efficacy testing.
2379-3708
Payne, Ruth O.
af14315a-cd57-4c77-b2bc-4d03d0daf6d7
Silk, Sarah
cd15636e-1e31-400b-af5c-ddfba66da60b
Elias, Sean
d86110c2-2c85-4c50-aab3-1ca6ef975f6a
Miura, Kazutoyo
37aa1488-b065-4302-b465-25b2c6dcb5b1
Diouf, Ababacar
1f14c20b-47d5-4c49-81c6-cc8de844f36b
Galaway, Francis
5f87d8e3-4f31-4461-a5ff-cf27b718c8b3
De Graaf, Hans
447e78ed-346f-45bb-9238-fce2118d5559
Brendish, Nathan J.
d07b588f-4919-456d-8604-04efde7711fd
Poulton, Ian D.
65ad53bb-91b1-4e68-be0b-45f04a69318e
Griffiths, Oliver J.
82530471-6a0f-4ca0-80de-dd4b66c0167b
Edwards, Nick J.
47ec5e93-25a1-4eea-a919-8c3f5e9c9e37
Jin, Jing
fa4bc2a9-e223-41f1-bf01-af27aa6af9c2
Labbe, Genevieve M.
453e8154-d4cd-429e-9b4e-8be7be260cf0
Alanine, Daniel G.W.
3120445a-8ef0-4a4f-b6b5-a9f02fde36c3
Siani, Loredana
e32d7a9d-1389-460f-8feb-3be5162f1671
Di Marco, Stefania
68ec50d7-c329-49d3-af2e-830435f28c1a
Roberts, Rachel
00128330-2392-4745-9b49-7c61330ff42a
Green, Nicky
faeb946a-4382-441a-a308-eceb9a13ce40
Berrie, Eleanor
030f38f4-ab0f-4b89-8e3f-bfc447d6387b
Ishizuka, Andrew
5a6f7e64-a284-4815-96ca-b9074d665c18
Nielsen, Carolyn M.
b4efeed7-92bc-4616-bd2f-92ce5aba55ff
Bardelli, Martino
2c885d03-69ce-4e76-a25b-2a7d7592acd4
Partey, Frederica D.
703d7cb9-b8b3-469b-9143-b59448064719
Ofori, Michael F.
09898aed-883d-4dde-a313-6e3d83ce737b
Barford, Lea
4a1f1ada-7d2e-4167-90bd-7a8e71250047
Wambua, Juliana
ed1caa7c-9df8-408b-b7f0-d43a9059da43
Murungi, Linda M.
df67b49a-211f-4d8b-a776-0cd04aed272f
Osier, Faith H.
8f99b473-594a-43a6-aa03-b0f9b5c1bf92
Biswas, Sumi
ac3e43ac-7cb7-4024-986f-6ec503e7fcae
McCarthy, James S.
2db9edc8-70c2-471e-8bf5-64560749604b
Minassian, Angela M.
93984419-d2e6-48fc-ad3c-9126d9a19e7c
Ashfield, Rebecca
bc4e87b2-6c8f-41df-977e-0046ee9fe13a
Viebig, Nicola K.
5f4b7d5b-afdb-40b7-b807-d3ebc7e02a6c
Nugent, Fay L.
c526acc8-fa2b-4052-8004-9d1721fc1bc7
Douglas, Alexander D.
443ef0ce-d9df-4121-85ed-2014d726f5d8
Vekemans, Johan
3fbbbbb8-6ce6-4aa2-ab2f-3839d23f3e2c
Wright, Gavin J.
23523ba4-c196-4afc-b3a6-f9d3f0bc4cbf
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Hill, Adrian V.S.
dc9fe6a9-92c5-42f9-98e7-2eca1201c13c
Long, Carole A.
0a762300-9d7a-47d0-b086-78676f736540
Lawrie, Alison M.
dd354ff4-6d60-4029-af83-ae6d233eb2af
Draper, Simon J.
e874c36e-5bad-4acf-8f55-41fa7c871464
Payne, Ruth O.
af14315a-cd57-4c77-b2bc-4d03d0daf6d7
Silk, Sarah
cd15636e-1e31-400b-af5c-ddfba66da60b
Elias, Sean
d86110c2-2c85-4c50-aab3-1ca6ef975f6a
Miura, Kazutoyo
37aa1488-b065-4302-b465-25b2c6dcb5b1
Diouf, Ababacar
1f14c20b-47d5-4c49-81c6-cc8de844f36b
Galaway, Francis
5f87d8e3-4f31-4461-a5ff-cf27b718c8b3
De Graaf, Hans
447e78ed-346f-45bb-9238-fce2118d5559
Brendish, Nathan J.
d07b588f-4919-456d-8604-04efde7711fd
Poulton, Ian D.
65ad53bb-91b1-4e68-be0b-45f04a69318e
Griffiths, Oliver J.
82530471-6a0f-4ca0-80de-dd4b66c0167b
Edwards, Nick J.
47ec5e93-25a1-4eea-a919-8c3f5e9c9e37
Jin, Jing
fa4bc2a9-e223-41f1-bf01-af27aa6af9c2
Labbe, Genevieve M.
453e8154-d4cd-429e-9b4e-8be7be260cf0
Alanine, Daniel G.W.
3120445a-8ef0-4a4f-b6b5-a9f02fde36c3
Siani, Loredana
e32d7a9d-1389-460f-8feb-3be5162f1671
Di Marco, Stefania
68ec50d7-c329-49d3-af2e-830435f28c1a
Roberts, Rachel
00128330-2392-4745-9b49-7c61330ff42a
Green, Nicky
faeb946a-4382-441a-a308-eceb9a13ce40
Berrie, Eleanor
030f38f4-ab0f-4b89-8e3f-bfc447d6387b
Ishizuka, Andrew
5a6f7e64-a284-4815-96ca-b9074d665c18
Nielsen, Carolyn M.
b4efeed7-92bc-4616-bd2f-92ce5aba55ff
Bardelli, Martino
2c885d03-69ce-4e76-a25b-2a7d7592acd4
Partey, Frederica D.
703d7cb9-b8b3-469b-9143-b59448064719
Ofori, Michael F.
09898aed-883d-4dde-a313-6e3d83ce737b
Barford, Lea
4a1f1ada-7d2e-4167-90bd-7a8e71250047
Wambua, Juliana
ed1caa7c-9df8-408b-b7f0-d43a9059da43
Murungi, Linda M.
df67b49a-211f-4d8b-a776-0cd04aed272f
Osier, Faith H.
8f99b473-594a-43a6-aa03-b0f9b5c1bf92
Biswas, Sumi
ac3e43ac-7cb7-4024-986f-6ec503e7fcae
McCarthy, James S.
2db9edc8-70c2-471e-8bf5-64560749604b
Minassian, Angela M.
93984419-d2e6-48fc-ad3c-9126d9a19e7c
Ashfield, Rebecca
bc4e87b2-6c8f-41df-977e-0046ee9fe13a
Viebig, Nicola K.
5f4b7d5b-afdb-40b7-b807-d3ebc7e02a6c
Nugent, Fay L.
c526acc8-fa2b-4052-8004-9d1721fc1bc7
Douglas, Alexander D.
443ef0ce-d9df-4121-85ed-2014d726f5d8
Vekemans, Johan
3fbbbbb8-6ce6-4aa2-ab2f-3839d23f3e2c
Wright, Gavin J.
23523ba4-c196-4afc-b3a6-f9d3f0bc4cbf
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Hill, Adrian V.S.
dc9fe6a9-92c5-42f9-98e7-2eca1201c13c
Long, Carole A.
0a762300-9d7a-47d0-b086-78676f736540
Lawrie, Alison M.
dd354ff4-6d60-4029-af83-ae6d233eb2af
Draper, Simon J.
e874c36e-5bad-4acf-8f55-41fa7c871464

Payne, Ruth O., Silk, Sarah, Elias, Sean, Miura, Kazutoyo, Diouf, Ababacar, Galaway, Francis, De Graaf, Hans, Brendish, Nathan J., Poulton, Ian D., Griffiths, Oliver J., Edwards, Nick J., Jin, Jing, Labbe, Genevieve M., Alanine, Daniel G.W., Siani, Loredana, Di Marco, Stefania, Roberts, Rachel, Green, Nicky, Berrie, Eleanor, Ishizuka, Andrew, Nielsen, Carolyn M., Bardelli, Martino, Partey, Frederica D., Ofori, Michael F., Barford, Lea, Wambua, Juliana, Murungi, Linda M., Osier, Faith H., Biswas, Sumi, McCarthy, James S., Minassian, Angela M., Ashfield, Rebecca, Viebig, Nicola K., Nugent, Fay L., Douglas, Alexander D., Vekemans, Johan, Wright, Gavin J., Faust, Saul N., Hill, Adrian V.S., Long, Carole A., Lawrie, Alison M. and Draper, Simon J. (2017) Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions. JCI Insight, 2 (21). (doi:10.1172/jci.insight.96381).

Record type: Article

Abstract

The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen — a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers. We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been induced by immunization in humans, with levels greatly exceeding the serum antibody responses observed in African adults following years of natural malaria exposure. These data support the progression of RH5-based vaccines to human efficacy testing.

Text
170921 VAC057 manuscript Payne et al clean - Accepted Manuscript
Restricted to Repository staff only
Request a copy
Text
JCI Insight96381 VAC057 published - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 5 October 2017
e-pub ahead of print date: 2 November 2017

Identifiers

Local EPrints ID: 417223
URI: https://eprints.soton.ac.uk/id/eprint/417223
ISSN: 2379-3708
PURE UUID: bd3fb28b-fe5e-46e1-b837-8963c74a33c0
ORCID for Nathan J. Brendish: ORCID iD orcid.org/0000-0002-9589-4937
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 26 Jan 2018 17:30
Last modified: 14 Mar 2019 01:41

Export record

Altmetrics

Contributors

Author: Ruth O. Payne
Author: Sarah Silk
Author: Sean Elias
Author: Kazutoyo Miura
Author: Ababacar Diouf
Author: Francis Galaway
Author: Hans De Graaf
Author: Nathan J. Brendish ORCID iD
Author: Ian D. Poulton
Author: Oliver J. Griffiths
Author: Nick J. Edwards
Author: Jing Jin
Author: Genevieve M. Labbe
Author: Daniel G.W. Alanine
Author: Loredana Siani
Author: Stefania Di Marco
Author: Rachel Roberts
Author: Nicky Green
Author: Eleanor Berrie
Author: Andrew Ishizuka
Author: Carolyn M. Nielsen
Author: Martino Bardelli
Author: Frederica D. Partey
Author: Michael F. Ofori
Author: Lea Barford
Author: Juliana Wambua
Author: Linda M. Murungi
Author: Faith H. Osier
Author: Sumi Biswas
Author: James S. McCarthy
Author: Angela M. Minassian
Author: Rebecca Ashfield
Author: Nicola K. Viebig
Author: Fay L. Nugent
Author: Alexander D. Douglas
Author: Johan Vekemans
Author: Gavin J. Wright
Author: Saul N. Faust ORCID iD
Author: Adrian V.S. Hill
Author: Carole A. Long
Author: Alison M. Lawrie
Author: Simon J. Draper

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×