A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques.

  title={A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques.},
  author={Peng Zhang and Elisabeth Narayanan and Qingbo Liu and Yaroslav I Tsybovsky and Kristin L. Boswell and Shilei Ding and Zonghui Hu and Dean A. Follmann and Yin Lin and Huiyi Miao and Hana Schmeisser and Denise Rogers and Samantha Falcone and Sayda M. Elbashir and Vladimir Presnyak and Kapil Bahl and Madhu S. Prabhakaran and Xuejun Chen and Edward K. Sarfo and David R. Ambrozak and Rajeev Gautam and MA Martin and Joanna Swerczek and Richard Herbert and Deborah E. Weiss and Johnathan Misamore and Giuseppe Ciaramella and Sunny Himansu and Guillaume B. E. Stewart-Jones and Adrian B. McDermott and Richard A. Koup and John R. Mascola and Andr{\'e}s Finzi and Andrea Carfi and Anthony S. Fauci and Paolo Lusso},
  journal={Nature medicine},
The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in… 

CD4-binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wildtype animals

G germline-targeting of IOMA-class antibody precursors represents a potential vaccine strategy to induce CD4bs bNAbs, and cloned antibodies overcame neutralization roadblocks including accommodating the N276gp120 glycan.

Implications of the 375W mutation for HIV-1 tropism and vaccine development

Increased sCD4 sensitivity and enhanced macrophage infection provide strong evidence that 375W confers exposure of the CD4bs across Envs from different clades/CRF/cpx and disease stages, and 375W is an ideal substitution for inclusion into HIV vaccines constructed from different subtype Envs.

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies

Strategies for the induction of potent and broad HIV-1 bnAbs are discussed and the steps that may be necessary for ultimate success are outlined.

SARS-CoV-2 Virus-like Particles Produced by a Single Recombinant Baculovirus Generate Anti-S Antibody and Protect against Variant Challenge

The generation of SARS-CoV-2 VLPs by the co-expression of the salient structural proteins in insect cells using the established baculovirus expression system is described and suggested to offer an efficient vaccine that mitigates against virus load and prevents severe disease.

Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation

This study derived two HIV-1 Env variants that are enriched in state 1 and can be efficiently cross-linked to maintain this shape, and provides a path to a better characterization of the native pretriggered Env, which should assist vaccine development.

Transduction of HEK293 Cells with BacMam Baculovirus Is an Efficient System for the Production of HIV-1 Virus-like Particles

This work puts the basis for future studies aiming at scaling up the BacMam baculovirus system as an alternative strategy for VLP production by determining the optimal conditions of multiplicity of infection (MOI), viable cell density (VCD) at infection, and butyric acid (BA) concentration that maximize cell transduction and V LP production.

Human vaccines & immunotherapeutics: news December 2021

  • Biology, Medicine
    Human vaccines & immunotherapeutics
  • 2022
Tests of Omicron neutralization by sera of vaccinated individuals indicates that the mRNA vaccines BNT162b2 and mRNA-1273 protect from disease caused by this variant but only after the full three-dose course and with reduced efficacy compared to activity on the Delta strain.

mRNA-based modalities for infectious disease management

The unique properties of mRNA-based vaccines for infectious diseases, delivery technologies, discussed current challenges, and highlighted the prospects of this promising technology in the future are summarized.



Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

It is found that immunization of rhesus macaques with thepentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian–human immunodeficiency virus (SHIV) challenge.

Antibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates

Compared Env antibody responses in BG505 SOSIP-immunized NHPs with those in BG 505 SHIV-infected NHPs, by analyzing monoclonal antibodies (mAbs), new insights are provided into the antibody response against BG505 Env during infection and immunization and limitations that need to be overcome to induce better responses after vaccination are provided.

HIV-1 neutralizing antibodies induced by native-like envelope trimers

A major goal of HIV-1 vaccine development is to identify immunogens capable of inducing protective titers of broadly neutralizing antibodies (bNAbs) against circulating, neutralization-resistant (tier 2) viruses, and soluble, recombinant trimers based on the BG505 clade A and B41 clade B tier 2 viruses are engineered.

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

Next-generation liposome-based adjuvant can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection, and future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.

Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques

These findings identify Env–rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors.