Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection

Mitchell, Julie L.; Pollara, Justin; Dietze, Kenneth; Edwards, R. Whitney; Nohara, Junsuke; N’guessan, Kombo F.; Zemil, Michelle; Buranapraditkun, Supranee; Takata, Hiroshi; Li, Yifan; Muir, Roshell; Kroon, Eugène; Pinyakorn, Suteeraporn; Jha, Shalini; Manasnayakorn, Sopark; Chottanapund, Suthat; Thantiworasit, Pattarawat; Prueksakaew, Peeriya; Ratnaratorn, Nisakorn; Nuntapinit, Bessara; Fox, Lawrence; Tovanabutra, Sodsai; Paquin‐Proulx, Dominic; Wieczorek, Lindsay; Polonis, Victoria R.; Maldarelli, Frank; Haddad, Elias K.; Phanuphak, Praphan; Sacdalan, Carlo; Rolland, Morgane; Ananworanich, Jintanat; Vasan, Sandhya; Ferrari, Guido; Trautmann, Lydie

doi:10.1172/jci150937

Cited by 10 publications

(9 citation statements)

References 66 publications

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“…Therefore, our results suggest that Tfh cells have a limited role when plasma viremia peaks but are major contributors to the set point viremia. This is also supported by the delayed formation of germinal centers in SIV-infected macaques ( 37 ) and in HIV-infected individuals ( 38 ).…”

Section: Discussionmentioning

confidence: 79%

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Gantner

Buranapraditkun

Pagliuzza

et al. 2022

Preprint

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Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We analyzed productively and latently infected cells in blood and lymphoid tissue from individuals in acute infection. The phenotype of productively infected cells rapidly evolved with time and differed between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded/disseminated cells, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells in blood and lymph nodes and latently infected cells are generated simultaneously.One-Sentence SummaryHIV initially infects phenotypically and clonotypically distinct T cells and establishes a latent reservoir concomitantly.

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Section: Discussionmentioning

confidence: 79%

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Gantner

Buranapraditkun

Pagliuzza

et al. 2022

Preprint

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“…In addition, HIV-1 virions can be trapped and retained in follicular dendritic cells for many months after ART initiation ( 30 ), leading to prolonged antigen availability within germinal centers. A recent study on the effect of early ART in individuals with acute infection reported that antibody development persisted during suppressive ART ( 31 ), but this study did not evaluate aNAb responses and did not include a treatment interruption. In this study, we assessed the aNAb responses of 12 early-treated individuals, including the viral and plasma samples from pre-ART and early and late post-ATI time points.…”

Section: Discussionmentioning

confidence: 99%

Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption

Esmaeilzadeh,

Etemad,

Lavine

et al. 2023

Sci. Transl. Med.

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Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.

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“…Previous studies have shown that HIV-1 Env-reactive antibodies persist in the absence of viremia for individuals on anti-retroviral therapy, but the B-cell subsets were not fully defined ( 72 , 73 ). Interestingly, one viremia controller (V253) generated plasma heterologous HIV-1 nAbs during late timepoints of SHIV infection, thus raising the hypothesis of neutralizing B-cell maturation in the absence of circulating viremia, which could be mimicked by cART.…”

Section: Discussionmentioning

confidence: 99%

Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection

Evangelous,

Berry,

Venkatayogi

et al. 2023

J Virol

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We recently found that a new pathogenic chimeric simian-human immunodeficiency virus (SHIV) elicited heterologous human immunodeficiency virus type-1 (HIV-1) neutralizing antibodies (nAbs) in therapy-naïve young rhesus macaques (RMs) following neonatal SHIV infection. Moreover, a subset of the SHIV-infected young RMs spontaneously controlled viremia. Here we evaluated humoral and cellular immunity and plasma biomarkers associated with spontaneous viremia suppression in a new model of young SHIV-infected RMs that generated heterologous HIV-1 nAbs independent of viremia control to gain insights into pediatric immunity that may be harnessed by appropriate therapies in HIV-1-infected infants and children. We determined the levels of 31 plasma analytes (cytokines, chemokines, and growth factors) in SHIV-infected RMs over the course of infection and found that six analytes with chemoattractant or pro-inflammatory activities had significantly lower levels in plasma of RMs that controlled viremia compared to non-controllers. Single-cell transcriptomics of blood-derived immune cells demonstrated that RMs with viremia control had upregulated genes associated with immune activation and cytotoxic functions, whereas non-controllers had upregulated genes associated with immune cell exhaustion and dysfunction. In addition to CD8 T and natural killer cells, monocytes with upregulation of inhibitory genes previously reported only in cytotoxic cells constituted the immunologic environment associated with viremia suppression. These data implicated a complex immunologic milieu of viremia suppression that is not fully defined in pediatric subjects. Understanding immune cell subsets that may be harnessed to control viremia will provide insights into future designs of HIV-1 therapeutic strategies. IMPORTANCE Despite the advent of highly active anti-retroviral therapy, people are still dying from HIV-related causes, many of whom are children, and a protective vaccine or cure is needed to end the HIV pandemic. Understanding the nature and activation states of immune cell subsets during infection will provide insights into the immunologic milieu associated with viremia suppression that can be harnessed via therapeutic strategies to achieve a functional cure, but these are understudied in pediatric subjects. We evaluated humoral and adaptive host immunity associated with suppression of viremia in rhesus macaques infected soon after birth with a pathogenic SHIV. The results from our study provide insights into the immune cell subsets and functions associated with viremia control in young macaques that may translate to pediatric subjects for the design of future anti-viral strategies in HIV-1-infected infants and children and contribute to an understudied area of HIV-1 pathogenesis in pediatric subjects.

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Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection

Cited by 10 publications

References 66 publications

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption

Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection

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