Broadly neutralizing antibodies and vaccine design against HIV-1 infection

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Abstract

Remarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

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Rational HIV immunogen design to target specific germline B cell receptors.

Joseph Jardine, Jean-Philippe Julien, Sergey Menis … (2013)

Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.

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The immune response during acute HIV-1 infection: clues for vaccine development

Andrew J. McMichael, Persephone Borrow, Georgia D. Tomaras … (2009)

Key Points The early virological factors in HIV-1 infection, including transmission and the nature of the founder virus, can affect the time course of viraemia through the early peak to set point. The identification of patients within the first few weeks of HIV-1 infection has provided early evidence of immune system damage, including massive apoptosis of CD4+ T cells, which is associated with the presence of apoptotic microparticles and TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) in the blood, and damage to germinal centres in mucosal lymphoid tissues. The first innate immune responses include the appearance of acute-phase proteins, early cytokine storm and activation of natural killer (NK) cells. An innate immune response to HIV-1 can be damaging, however, as it can draw susceptible T cells to the infection foci. The first T cell response controls the founder virus by killing infected T cells. However, the T cell response also selects mutational changes in the founder virus, allowing immune evasion. The first B cell response consists of early immune complexes, followed by non-neutralizing antibodies against the founder virus and then the slow development of broadly acting neutralizing antibodies. Development of vaccines that rapidly induce broadly acting neutralizing antibodies might be beneficial in preventing HIV infection. Understanding the early events and immune responses is crucial to devising vaccine strategies that can improve the weak protection offered by current HIV vaccines that are being trialled, such as the RV144 (Thai) efficacy trial.

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Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan … (2009)

The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.) 2009 Massachusetts Medical Society

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Author and article information

Contributors

Linqi Zhang: zhanglinqi@tsinghua.edu.cn

Journal

Journal ID (nlm-ta): Front Med

Journal ID (iso-abbrev): Front Med

Title: Frontiers of Medicine

Publisher: Higher Education Press (Beijing )

ISSN (Print): 2095-0217

ISSN (Electronic): 2095-0225

Publication date (Electronic): 19 December 2019

Publication date PMC-release: 19 December 2019

Publication date (Print): 2020

Volume: 14

Issue: 1

Pages: 30-42

Affiliations

GRID grid.12527.33, ISNI 0000 0001 0662 3178, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, , Tsinghua University, ; Beijing, 100084 China

Article

Publisher ID: 721

DOI: 10.1007/s11684-019-0721-9

PMC ID: 8320319

PubMed ID: 31858368

SO-VID: f7af98ba-3560-43f1-b585-55c2b3875500

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

History

Date received : 4 August 2019

Date accepted : 7 September 2019

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Keywords: hiv-1,broadly neutralizing antibodies,env conformational states,vaccine design,sosip

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Keywords: hiv-1, broadly neutralizing antibodies, env conformational states, vaccine design, sosip

Broadly neutralizing antibodies and vaccine design against HIV-1 infection

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Malaria vaccine development

Most cited references 121

Rational HIV immunogen design to target specific germline B cell receptors.

The immune response during acute HIV-1 infection: clues for vaccine development

Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

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