HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

Pernas, María; Sánchez-Merino, Víctor; Casado, Concepción; Merino-Mansilla, Alberto; Olivares, Isabel; Yuste, Eloísa; López-Galı́ndez, Cecilio

doi:10.1371/journal.pone.0134054

Cited by 5 publications

(7 citation statements)

References 23 publications

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“…The role of viral diversity driving bNAb induction has been previously described in chronically infected patients (54)(55)(56). In the present study, we have observed in patients within the first year of HIV-1 infec-…”

Section: Discussionsupporting

confidence: 68%

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sánchez-Merino

Fabra-García

Gonzàlez

et al. 2016

J Virol

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A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel IMPORTANCEThere are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier than previously thought. The identification of HIV-1-infected patients with these activities within the first months of infection and characterization of these responses will help in defining new immunogen designs and neutralization targets for vaccine-mediated induction of bNAbs. O ne of the main challenges for the development of a preventive human immunodeficiency virus type 1 (HIV-1) vaccine is the design of immunogens and immunization strategies that allow the induction of neutralizing antibody responses against multiple HIV-1 isolates. The main target of neutralizing antibodies is the trimeric envelope glycoprotein spike (Env). Unfortunately, when these recombinant proteins are used as immunogens, there is minimal induction of cross-reactive neutralizing antibody responses (1, 2). Despite these hurdles, high titers of broadly neutralizing antibodies (bNAbs) have been found in some chronically infected patients (3, 4). Data from many studies indicate that between 10 and 25% of patient sera displayed broadly neutralizing capacity against diverse HIV-1 strains (2-5), and one large study showed that 50% of sera from chronic infection can neutralize 50% of virus strains (6). Antibody responses have been studied extensively in these chronically infected patients, new bNAbs have been isolated, and the molecular determinants recognized by these antibodies have been characterized. Although these antibodies do not protect infected patients, they exert selective pressure on the virus (7-9). On the other hand, and more importantly, passive transfer of broadly neutralizing antibodies to monkeys and humanized mice effectively protects them against chimeric simianhuman immunodeficiency virus (SHIV) infection and HIV infection, respectively (10-18). Additionally, promising results have been obtained in recent years with approaches based on the production of broadly neutralizing antibodies against HIV and SHIV, or molecules resembling these antibodies, by adeno-associated vectors in animal models (19,20). In humans, passive transfer of bNAbs also has shown some efficacy in controlling viral replication in two recent studies, showing that passive transfer of mono-

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Section: Discussionsupporting

confidence: 68%

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sánchez-Merino

Fabra-García

Gonzàlez

et al. 2016

J Virol

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“…The occurrence of SI several years after primary infection of NYU6501 may have hit an already impaired immune system, not able to further boost the antibody response. In addition to the timing of SI, viral diversity was shown to correlate with the development of a strong immune response [ 13 , 14 ]. Of interest, NYU6564 is both stimulated with a genetically more distant strain compared to NYU6501 (20% versus 17%) and also comes up with diverse env populations post-SI.…”

Section: Discussionmentioning

confidence: 99%

“…Since SI cannot be accurately timed in NYU6501, diversity data immediately post-SI remains obscure. It is possible that the short interval of ART during pregnancy lowered viral load and diversity, both known to drive a strong immune response [ 13 , 14 , 51 ]. The genetic distance analysis of NYU6501 further revealed that the new population detected after SI significantly differs in env and gag , but not in pol with a distance of only 2% compared to viruses pre-SI.…”

Section: Discussionmentioning

confidence: 99%

“…However, the secondary challenge of the immune system by a SI event can boost a strong immune response, as observed for various cases of SI with a different subtype (intersubtype SI) [ 11 , 12 ]. The increased breadth and potency of the heterologous neutralizing antibody (nAb) response has been attributed to the elevated antigenic stimulation with diverse strains [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…So far, intrasubtype SI studies have mainly covered subtypes B [ 14 , 16 , 18 , 19 , 21 , 22 ], C [ 5 , 15 , 20 ], and A [ 10 , 12 ]. Here we characterize two cases of CRF02_AG intrasubtype SI found in Cameroon [ 11 , 23 ] using a novel Next-Generation Sequencing (NGS) method and describe the longitudinal impact on the adaptive immune response.…”

Section: Introductionmentioning

confidence: 99%

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Contrasting antibody responses to intrasubtype superinfection with CRF02_AG

et al. 2017

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HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.

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HIV controllers suppress viral replication and evolution and prevent disease progression following intersubtype HIV-1 superinfection

Azevedo

Delatorre

Côrtes

et al. 2019

Aids

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HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity

Cited by 5 publications

References 23 publications

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Contrasting antibody responses to intrasubtype superinfection with CRF02_AG

HIV controllers suppress viral replication and evolution and prevent disease progression following intersubtype HIV-1 superinfection

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