Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention

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Abstract

Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for blocking acquisition of HIV-1 infection. Clinical trials are currently underway to evaluate the efficacy of two vaccine candidates and a broadly neutralizing antibody (bNAb) to prevent HIV-1 infection in humans. However, the vast diversity of HIV-1 is a major challenge for both active and passive immunization. Here we review current immunologic strategies for HIV-1 prevention, with a focus on current and next-generation vaccines and bNAbs.

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Most cited references 103

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Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

Myron S Cohen, Ying Q Chen, Marybeth McCauley … (2016)

An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

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The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

Nilu Goonetilleke, Michael K.P. Liu, Jesus Salazar-Gonzalez … (2009)

Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1–specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell–driven escape.

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HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis.

M. Juliana McElrath, Stephen De Rosa, Zoe Moodie … (2008)

In the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not reduce plasma viraemia after infection, and HIV-1 incidence was higher in vaccine-treated than in placebo-treated men with pre-existing adenovirus serotype 5 (Ad5) immunity. We assessed vaccine-induced immunity and its potential contributions to infection risk. To assess immunogenicity, we characterised HIV-specific T cells ex vivo with validated interferon-gamma ELISPOT and intracellular cytokine staining assays, using a case-cohort design. To establish effects of vaccine and pre-existing Ad5 immunity on infection risk, we undertook flow cytometric studies to measure Ad5-specific T cells and circulating activated (Ki-67+/BcL-2(lo)) CD4+ T cells expressing CCR5. We detected interferon-gamma-secreting HIV-specific T cells (range 163/10(6) to 686/10(6) peripheral blood mononuclear cells) ex vivo by ELISPOT in 77% (258/354) of people receiving vaccine; 218 of 354 (62%) recognised two to three HIV proteins. We identified HIV-specific CD4+ T cells by intracellular cytokine staining in 58 of 142 (41%) people. In those with reactive CD4+ T cells, the median percentage of CD4+ T cells expressing interleukin 2 was 88%, and the median co-expression of interferon gamma or tumor necrosis factor alpha (TNFalpha), or both, was 72%. We noted HIV-specific CD8+ T cells (range 0.4-1.0%) in 117 of 160 (73%) participants, expressing predominantly either interferon gamma alone or with TNFalpha. Vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile, did not differ between vaccinated male cases (before infection) and non-cases. Ad5-specific T cells were lower in cases than in non-cases in several subgroup analyses. The percentage of circulating Ki-67+BcL-2(lo)/CCR5+CD4+ T cells did not differ between cases and non-cases. Consistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells. Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial.

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Author and article information

Journal

Title: Annual Review of Immunology

Abbreviated Title: Annu. Rev. Immunol.

Publisher: Annual Reviews

ISSN (Print): 0732-0582

ISSN (Electronic): 1545-3278

Publication date Created: April 26 2020

Publication date (Print): April 26 2020

Volume: 38

Issue: 1

Pages: 673-703

Affiliations

[1 ]Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA;

[2 ]Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, Massachusetts 02114, USA

[3 ]Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA

[4 ]New Mexico Consortium, Los Alamos, New Mexico 87545, USA

Article

DOI: 10.1146/annurev-immunol-080219-023629

PubMed ID: 32340576

SO-VID: ebb8305e-9069-49ae-a5c5-32b3cd0da725

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ScienceOpen disciplines: Medicine,Cell biology,Immunology,Human biology,Microbiology & Virology,Life sciences

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ScienceOpen disciplines: Medicine, Cell biology, Immunology, Human biology, Microbiology & Virology, Life sciences

Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention

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Abstract

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Annual Reviews HIV/AIDS: Public Health and Society

Most cited references 103

Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis.

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