Development of a two-component nanoparticle vaccine displaying an HIV-1 envelope glycoprotein that elicits tier 2 neutralising antibodies

DOI: 10.3390/vaccines12091063

Authors: Kegomoditswe Malebo (University of Cape Town) , Jeremy Woodward (University of Cape Town) , Phindile Ximba (University of Cape Town) , Qiniso Mkhize (University of the Witwatersrand; National Institute for Communicable Diseases of the National Health Laboratory Services (South Africa)) , Sanele Cingo (University of Cape Town) , Thandeka Moyo-Gwete (University of the Witwatersrand; National Institute for Communicable Diseases of the National Health Laboratory Services (South Africa)) , Penny L. Moore (University of the Witwatersrand; National Institute for Communicable Diseases of the National Health Laboratory Services (South Africa); Centre for the AIDS Programme of Research in South Africa) , Anna-Lise Williamson (University of Cape Town) , Rosamund Chapman (University of Cape Town)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Vaccines , VOL 12

State: Published (Approved)
Published: September 2024
Diamond Proposal Number(s): 24039

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.

Journal Keywords: nanoparticle; mi3; CAP255; DNA; tier 2 neutralising antibodies; human immunodeficiency virus; prime-boost; vaccine

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios IV-Titan Krios IV at Diamond

Added On: 22/09/2024 10:48

Documents:
vaccines-12-01063.pdf

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Structural biology Nanoscience/Nanotechnology Drug Discovery Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)