Back to Search Start Over

Development of a Two-Component Nanoparticle Vaccine Displaying an HIV-1 Envelope Glycoprotein that Elicits Tier 2 Neutralising Antibodies

Authors :
Kegomoditswe Malebo
Jeremy Woodward
Phindile Ximba
Qiniso Mkhize
Sanele Cingo
Thandeka Moyo-Gwete
Penny L. Moore
Anna-Lise Williamson
Rosamund Chapman
Source :
Vaccines, Vol 12, Iss 9, p 1063 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Despite treatment and other interventions, an effective prophylactic HIV vaccine is still an essential goal in the control of HIV. Inducing robust and long-lasting antibody responses is one of the main targets of an HIV vaccine. The delivery of HIV envelope glycoproteins (Env) using nanoparticle (NP) platforms has been shown to elicit better immunogenicity than soluble HIV Env. In this paper, we describe the development of a nanoparticle-based vaccine decorated with HIV Env using the SpyCatcher/SpyTag system. The Env utilised in this study, CAP255, was derived from a transmitted founder virus isolated from a patient who developed broadly neutralising antibodies. Negative stain and cryo-electron microscopy analyses confirmed the assembly and stability of the mi3 into uniform icosahedral NPs surrounded by regularly spaced CAP255 gp140 Env trimers. A three-dimensional reconstruction of CAP255 gp140 SpyTag–SpyCatcher mi3 clearly showed Env trimers projecting from the centre of each of the pentagonal dodecahedral faces of the NP. To our knowledge, this is the first study to report the formation of SpyCatcher pentamers on the dodecahedral faces of mi3 NPs. To investigate the immunogenicity, rabbits were primed with two doses of DNA vaccines expressing the CAP255 gp150 and a mosaic subtype C Gag and boosted with three doses of the NP-developed autologous Tier 2 CAP255 neutralising antibodies (Nabs) and low levels of heterologous CAP256SU NAbs.

Details

Language :
English
ISSN :
2076393X
Volume :
12
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.f66ab97b60f14884ae590f25fd767ae5
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines12091063