A Boost for HIV Vaccine Design

  title={A Boost for HIV Vaccine Design},
  author={Dennis R. Burton and Robin A. Weiss},
  pages={770 - 773}
Antibodies that potently neutralize almost all HIV isolates could aid the rational design of a vaccine. A major roadblock to the development of an effective vaccine against the human immunodeficiency virus (HIV-1) is the lack of an immunogen that elicits broadly protective antibodies (1). Passive transfer studies in animal models have associated protection with neutralizing antibodies and, encouragingly, serum studies show that a subset of HIV-infected individuals produces potent broadly… 
Designer antigens for elicitation of broadly neutralizing antibodies against HIV
This work has investigated a novel and systematic approach to produce (not screen for) potential bNAbs against HIV, and established the concept and the experimental system for producing formaldehyde‐fixed HIV DAGs that carry temperature‐arrested prefusion intermediates.
Passive Immunization against HIV/AIDS by Antibody Gene Transfer
The status of antibody gene transfer is surveyed, the revolutionary progress on isolation of extremely bnAbs is reviewed, and the pros and cons of VIP are discussed and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics are discussed.
Novel Immunogens based on the gp41 protein of Human Immunodeficiency Virus type 1 and Display Systems for their Affinity Maturation
A novel lentiviral display system based on HIV-1 was developed and gp41 was truncated N-terminally in order to dispose of immunodominant, non-neutralizing sites and enhance the exposure of conserved regions and its stabilization by zipper domains.
Immune Focusing and Enhanced Neutralization Induced by HIV-1 gp140 Chemical Cross-Linking
It is shown that a largely trimeric form of soluble Env can be stably cross-linked with glutaraldehyde (GLA) without global modification of antigenicity, and cross-linking favors antigen stability, imparts antigenic modifications that selectively refocus antibody specificity and improves induction of NAbs, and might be a useful strategy for future vaccine design.
Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1
It is proposed that iMab-based BibNAbs, such as PG9-iMab and PG16-i Mab, are promising candidates for passive immunization to prevent HIV-1 infection.
The expanding array of HIV broadly neutralizing antibodies
A clearer probable benefit of further bn Ab characterization is a greater understanding of key decision points in bnAb development within the anti-HIV immune response, which may lead to new insights into how to trigger bnAbs by immunization and more clearly define the challenges to using bn Abs as therapeutic agents.
Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein
An immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV- 1 and simian immunodeficiency virus (SIV) Envs is reported.
Two Closely Related Env Antigens from the Same Patient Elicited Different Spectra of Neutralizing Antibodies against Heterologous HIV-1 Isolates
Assessment of closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features found certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs.
Predicting HIV-1 broadly neutralizing antibody epitope networks using neutralization titers and a novel computational method
Computational methods were implemented to rapidly survey protein structures and predict epitope networks associated with response to individual monoclonal antibodies, which resulted in the identification and deeper understanding of immunological hotspots targeted by broadly neutralizing HIV-1 antibodies.


Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Three broadly neutralizing antibodies are identified, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike.
Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target
High-throughput screening has revealed two new broadly neutralizing antibodies from a clade A–infected donor in Africa, which exhibit great potency and are able to neutralize a wide range of viruses from many different clades.
Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01
The identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike.
The role of antibodies in HIV vaccines.
Current vaccine design efforts have focused on a more detailed understanding of these broadly neutralizing antibodies and their epitopes to inform the design of improved vaccines.
Toward an antibody-based HIV-1 vaccine.
  • J. Hoxie
  • Biology
    Annual review of medicine
  • 2010
Progress in understanding the host antibody response to HIV-1 is summarized and current strategies for applying this information to develop an effective vaccine are summarized.
Challenges for structure-based HIV vaccine design
Structural information on the virion-associated HIV envelope spike and of the precise interaction of broadly neutralizing mAbs with their epitopes clarifies the steric and geometric constraints faced by antibodies targeting conserved HIV epitopes.
Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals
This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity, and three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV- 1 neutralizing antibodies with potential for passive protection and template-based vaccine design.
Structural definition of a conserved neutralization epitope on HIV-1 gp120
A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.
Immunology and the elusive AIDS vaccine
Fundamental immunological questions that need to be answered to develop a protective HIV vaccine are outlined and the immediate need to harness a much broader scientific community to achieve this goal is outlined.