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Vaccines
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Advances in Antibody Based HIV-1 Vaccine Development
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Advances in Antibody Based HIV-1 Vaccine Development

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "HIV Vaccines".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 7822

Special Issue Editors

Dr. Christina B. Karsten

E-Mail Website
Guest Editor
Institute for Translational HIV Research, Universitätsklinikum Essen (AöR), 45147 Essen, Germany
Interests: HIV; vaccine; B cell response; neutralizing antibodies; nonneutralizing antibodies; system serology; immunogen design; viral glycosylation; SIV
Dr. Rob J. Center

E-Mail Website
Guest Editor
Burnet Institute, Melbourne 3004, Australia
Interests: vaccines; HCV; HIV; protein; antibody

Special Issue Information

Dear Colleagues,

Despite the great success of antiretroviral therapy, both in the treatment and prevention of HIV-1 infection, a vaccine is still urgently needed to end the epidemic. Intensive collaborative work in the last decade resulted in the isolation of antibodies from a subset of HIV-positive patients, that can potently neutralize a broad spectrum of primary HIV-1 isolates in vitro and protect from infection in animal models, advancing these broadly neutralizing antibodies (bnAbs) to clinical trials in recent years. In parallel, detailed structural characterizations of bnAbs in complex with HIV-1 envelope proteins (Env) gave insights into particular features of these antibodies and their epitopes. Unfortunately, HIV-1 Env immunogens derived from this knowledge were not able to date to induce bnAbs upon vaccination of humans or non-human primates. However, they can do so in certain species like camelids or cows, which naturally generate antibodies with special characteristics of bnAbs. Detailed immunological studies are being performed to understand the generation of bnAbs in patients with the aim to recapitulate the underlying mechanisms in vaccination approaches. A continuous coevolution of virus and antibodies driven by immunological escape mutants seems to be essential and serves as the basis for the generation of a series of Env immunogens for the next vaccine trials. Besides neutralization, Fc-mediated effector functions of antibodies are also important to control viremia by targeting cytotoxic immune activities to HIV-1 infected cells, thus potentially eliminating viral reservoirs in the body. In view of future therapeutic vaccine trials, the focus will be on choosing the right combinations of antibodies as well as delivery modes in order to achieve persisting and highly effective antibody concentrations. For prophylactic passive vaccine trials, bnAbs or derivatives may be particularly interesting to prevent infection in high risk cohorts. For classical active vaccination programs it has to be shown whether suitable Env immunogens can be identified that are able to stimulate naive B cell precursors in large populations to generate bnAbs.

Dr. Christina B. Karsten
Dr. Rob J. Center
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HIV-1 vaccine development
  • broadly neutralizing antibodies
  • natural vs. vaccine-induced antibody response
  • effector functions of antibodies
  • structure-based immunogen design
  • vectors for vaccine delivery
  • perspectives for clinical applications

Published Papers (2 papers)

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Research

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15 pages, 2432 KiB  
Article
Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity
by Seth H. Pincus, Ryan B. Craig, Lauren Weachter, Celia C. LaBranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, David C. Montefiori and Pamela A. Kozlowski
Vaccines 2021, 9(7), 774; https://doi.org/10.3390/vaccines9070774 - 12 Jul 2021
Cited by 5 | Viewed by 2781
Abstract
We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to [...] Read more.
We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to recombinant Env and their antiviral activities were compared to that of the parental mAbs and CD4, as well as to control mAbs. The CD4/7B2 constructs bind to both gp41 and gp140, as well as to native Env expressed on the surface of infected cells. These constructs deliver cytotoxic immunoconjugates to HIV-infected cells, but not as well as a mixture of 7B2 and sCD4, and opsonize for antibody-mediated phagocytosis. Most surprisingly, given that 7B2 neutralizes weakly, if at all, is that the chimeric CD4/7B2 immunoadhesins exhibit broad and potent neutralization of HIV, comparable to that of well-known neutralizing mAbs. These data add to the growing evidence that enhanced neutralizing activity can be obtained with bifunctional mAbs/immunoadhesins. The enhanced neutralization activity of the CD4/7B2 chimeras may result from cross-linking of the two Env subunits with subsequent inhibition of the pre-fusion conformational events that are necessary for entry. Full article
(This article belongs to the Special Issue Advances in Antibody Based HIV-1 Vaccine Development)
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Review

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33 pages, 1868 KiB  
Review
Post-Immune Antibodies in HIV-1 Infection in the Context of Vaccine Development: A Variety of Biological Functions and Catalytic Activities
by Anna Timofeeva, Sergey Sedykh and Georgy Nevinsky
Vaccines 2022, 10(3), 384; https://doi.org/10.3390/vaccines10030384 - 02 Mar 2022
Cited by 4 | Viewed by 4247
Abstract
Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic [...] Read more.
Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, β-casein, serum albumin, and some other natural substrates. Currently, there are various directions for the development of HIV-1 vaccines: stimulation of the immune response on the mucous membranes; induction of cytotoxic T cells, which lyse infected cells and hold back HIV-infection; immunization with recombinant Env proteins or vectors encoding Env; mRNA-based vaccines and some others. However, despite many attempts to develop an HIV-1 vaccine, none have been successful. Here we review the entire spectrum of antibodies found in HIV-infected patients, including neutralizing antibodies specific to various viral epitopes, as well as antibodies formed against various autoantigens, catalytic antibodies against autoantigens, and some viral proteins. We consider various promising targets for developing a vaccine that will not produce unwanted antibodies in vaccinated patients. In addition, we review common problems in the development of a vaccine against HIV-1. Full article
(This article belongs to the Special Issue Advances in Antibody Based HIV-1 Vaccine Development)
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