HIV-1 vaccine design through minimizing envelope metastability

L He, S Kumar, JD Allen, D Huang, X Lin, CJ Mann… - Science …, 2018 - science.org
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here,
we present a coherent vaccine strategy by minimizing metastability. For 10 strains across …

Automated design by structure-based stabilization and consensus repair to achieve prefusion-closed envelope trimers in a wide variety of HIV strains

R Rawi, L Rutten, YT Lai, AS Olia, S Blokland… - Cell reports, 2020 - cell.com
Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit
neutralizing responses against HIV-1 strains closely related to the immunizing trimer …

Development of a 3mut-apex-stabilized envelope trimer that expands HIV-1 neutralization breadth when used to boost fusion peptide-directed vaccine-elicited …

GY Chuang, YT Lai, JC Boyington, C Cheng… - Journal of …, 2020 - Am Soc Microbiol
ABSTRACT HIV-1 envelope (Env) trimers, stabilized in a prefusion-closed conformation, can
elicit humoral responses capable of neutralizing HIV-1 strains closely matched in sequence …

Structure-guided redesign increases the propensity of HIV Env to generate highly stable soluble trimers

J Guenaga, V Dubrovskaya, N De Val… - Journal of …, 2016 - Am Soc Microbiol
Due to high viral diversity, an effective HIV-1 vaccine will likely require Envs derived from
multiple subtypes to generate broadly neutralizing antibodies (bNAbs). Soluble Env mimics …

Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding

DW Kulp, JM Steichen, M Pauthner, X Hu… - Nature …, 2017 - nature.com
Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-
like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are …

Rational design of DNA-expressed stabilized native-like HIV-1 envelope trimers

Y Aldon, PF McKay, J Allen, G Ozorowski, RF Lévai… - Cell reports, 2018 - cell.com
Summary The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for
antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies …

Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability

L Kong, L He, N De Val, N Vora, CD Morris… - Nature …, 2016 - nature.com
The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and
neutralization. Despite advances in trimer design, the roots of Env trimer metastability …

Structure-based design of a soluble prefusion-closed HIV-1 Env trimer with reduced CD4 affinity and improved immunogenicity

GY Chuang, H Geng, M Pancera, K Xu… - Journal of …, 2017 - Am Soc Microbiol
ABSTRACT The HIV-1 envelope (Env) trimer is a target for vaccine design as well as a
conformational machine that facilitates virus entry by transitioning between prefusion-closed …

Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine …

YN Zhang, J Paynter, A Antanasijevic, JD Allen… - Nature …, 2023 - nature.com
Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope
glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) …

A universal approach to optimize the folding and stability of prefusion-closed HIV-1 envelope trimers

L Rutten, YT Lai, S Blokland, D Truan, IJM Bisschop… - Cell reports, 2018 - cell.com
The heavily glycosylated native-like envelope (Env) trimer of HIV-1 is expected to have low
immunogenicity, whereas misfolded forms are often highly immunogenic. High-quality …