The University of Southampton
University of Southampton Institutional Repository

Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques

Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques
Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques

During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.

2059-0105
Pratap, Payal P
240ae677-6803-43b3-b2cd-01f72683b65c
Cottrell, Christopher A
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Quinn, James
8e8da2cc-ef42-4fcb-b310-01a01bc49906
Carnathan, Diane G
9d53ae27-4935-4068-88c0-3b2db6c58ce2
Bader, Daniel L V
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Tran, Andy S
a6433714-3130-4c94-875b-3ce299a897b0
Enemuo, Chiamaka A
d84e435b-68e3-449e-b969-9b0709f9395c
Ngo, Julia T
1e915c5a-50d8-4da1-8c8e-b372bf073143
Richey, Sara T
e1f5db2b-212e-448b-a3a3-db3b013b3d23
Gao, Hongmei
4dbf6f50-fb2e-4f56-99f4-23e0fe8b2d69
Shen, Xiaoying
4f18b14f-78d8-4cbb-aa94-16d7a10035fb
Greene, Kelli M
b808b4a9-8ea9-4207-9a98-f603f4cf2be8
Hurtado, Jonathan
91875d1b-67e1-4489-bd97-acfe4e885bef
Michaels, Katarzyna Kaczmarek
732d930c-f051-458f-a2f2-f0bf6540c616
Ben-Akiva, Elana
f22ff6eb-31f9-4f08-b878-e1c99acff9cf
Lemnios, Ashley
b8843f73-8074-4409-9598-bea521a0bb00
Melo, Mariane B
b98d4670-f268-4712-96ee-88f239c58f3e
Allen, Joel D
c89d5569-7659-4835-b535-c9586e956b3a
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Briney, Bryan
727772a6-e9c1-4d88-b191-f2c5a487e426
Montefiori, David
e1f1e5f0-7bed-4994-81e2-7f1e0ff5663b
Silvestri, Guido
e61939c1-36b4-4537-868a-10aeeabdff33
Irvine, Darrell J
63f295b5-7d49-4c85-9e9b-4797cebf5f89
Crotty, Shane
2e6a17e5-1804-4444-af94-3b2df194bf4d
Ward, Andrew B
7b743524-72d4-448d-b645-11c55782b656
Pratap, Payal P
240ae677-6803-43b3-b2cd-01f72683b65c
Cottrell, Christopher A
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Quinn, James
8e8da2cc-ef42-4fcb-b310-01a01bc49906
Carnathan, Diane G
9d53ae27-4935-4068-88c0-3b2db6c58ce2
Bader, Daniel L V
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Tran, Andy S
a6433714-3130-4c94-875b-3ce299a897b0
Enemuo, Chiamaka A
d84e435b-68e3-449e-b969-9b0709f9395c
Ngo, Julia T
1e915c5a-50d8-4da1-8c8e-b372bf073143
Richey, Sara T
e1f5db2b-212e-448b-a3a3-db3b013b3d23
Gao, Hongmei
4dbf6f50-fb2e-4f56-99f4-23e0fe8b2d69
Shen, Xiaoying
4f18b14f-78d8-4cbb-aa94-16d7a10035fb
Greene, Kelli M
b808b4a9-8ea9-4207-9a98-f603f4cf2be8
Hurtado, Jonathan
91875d1b-67e1-4489-bd97-acfe4e885bef
Michaels, Katarzyna Kaczmarek
732d930c-f051-458f-a2f2-f0bf6540c616
Ben-Akiva, Elana
f22ff6eb-31f9-4f08-b878-e1c99acff9cf
Lemnios, Ashley
b8843f73-8074-4409-9598-bea521a0bb00
Melo, Mariane B
b98d4670-f268-4712-96ee-88f239c58f3e
Allen, Joel D
c89d5569-7659-4835-b535-c9586e956b3a
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Briney, Bryan
727772a6-e9c1-4d88-b191-f2c5a487e426
Montefiori, David
e1f1e5f0-7bed-4994-81e2-7f1e0ff5663b
Silvestri, Guido
e61939c1-36b4-4537-868a-10aeeabdff33
Irvine, Darrell J
63f295b5-7d49-4c85-9e9b-4797cebf5f89
Crotty, Shane
2e6a17e5-1804-4444-af94-3b2df194bf4d
Ward, Andrew B
7b743524-72d4-448d-b645-11c55782b656

Pratap, Payal P, Cottrell, Christopher A, Quinn, James, Carnathan, Diane G, Bader, Daniel L V, Tran, Andy S, Enemuo, Chiamaka A, Ngo, Julia T, Richey, Sara T, Gao, Hongmei, Shen, Xiaoying, Greene, Kelli M, Hurtado, Jonathan, Michaels, Katarzyna Kaczmarek, Ben-Akiva, Elana, Lemnios, Ashley, Melo, Mariane B, Allen, Joel D, Ozorowski, Gabriel, Crispin, Max, Briney, Bryan, Montefiori, David, Silvestri, Guido, Irvine, Darrell J, Crotty, Shane and Ward, Andrew B (2025) Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques. NPJ Vaccines, 10 (1), [200]. (doi:10.1038/s41541-025-01252-4).

Record type: Article

Abstract

During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.

Text
s41541-025-01252-4
Available under License Creative Commons Attribution.
Download (3MB)

More information

Accepted/In Press date: 1 August 2025
Published date: 20 August 2025
Additional Information: Publisher Copyright: © The Author(s) 2025.

Identifiers

Local EPrints ID: 506154
URI: http://eprints.soton.ac.uk/id/eprint/506154
ISSN: 2059-0105
PURE UUID: 9e49811a-8f58-4150-9b29-983d0bd8dc30
ORCID for Daniel L V Bader: ORCID iD orcid.org/0000-0002-1208-3507
ORCID for Joel D Allen: ORCID iD orcid.org/0000-0003-2547-968X
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 29 Oct 2025 17:38
Last modified: 30 Oct 2025 02:59

Export record

Altmetrics

Contributors

Author: Payal P Pratap
Author: Christopher A Cottrell
Author: James Quinn
Author: Diane G Carnathan
Author: Andy S Tran
Author: Chiamaka A Enemuo
Author: Julia T Ngo
Author: Sara T Richey
Author: Hongmei Gao
Author: Xiaoying Shen
Author: Kelli M Greene
Author: Jonathan Hurtado
Author: Katarzyna Kaczmarek Michaels
Author: Elana Ben-Akiva
Author: Ashley Lemnios
Author: Mariane B Melo
Author: Joel D Allen ORCID iD
Author: Gabriel Ozorowski
Author: Max Crispin ORCID iD
Author: Bryan Briney
Author: David Montefiori
Author: Guido Silvestri
Author: Darrell J Irvine
Author: Shane Crotty
Author: Andrew B Ward

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 http://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.

×