Neutralizing antibody patterns and viral escape in HIV-1 non-B subtype chronically infected treatment-naive individuals

Kelly, Halonna; Urbanski, Mateusz M.; Burda, Sherri; Zhong, Ping; Konings, Frank; Nanfack, Joseph; Tongo, Marcel; Kinge, Thompson; Achkar, Jacqueline M.; Nyambi, Phillipe N.

doi:10.3233/hab-2005-143-406

Cited by 8 publications

(14 citation statements)

References 7 publications

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“…In chronic infection breadth develops for heterologous tier 1 viruses and viruses can evolve in response to those nAbs (Haldar et al, 2011; Kelly et al, 2005; Nyambi et al, 2008). However, autologous virus-neutralizing mAbs isolated from HIV-1-infected people have been strictly strain-specific with no detectable heterologous tier 1 or tier 2 HIV-1 neutralization (Derdeyn et al, 2014) (DC Montefiori, personal communication).…”

Section: Discussionmentioning

confidence: 99%

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

Moody

Gao

Gurley

et al. 2015

Cell Host & Microbe

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Summary The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

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Section: Discussionmentioning

confidence: 99%

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

Moody

Gao

Gurley

et al. 2015

Cell Host & Microbe

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“…Stocks of viruses were prepared in HIVnegative donor PBMCs over a 2-week period as previously described, 7,13 titrated in GHOST cells, and tested in the GHOST cell neutralization assays as described below and in previous studies. 14,15 Plasma A panel of 10 heterologous plasma and two sera (FDA-2 and UCLA) obtained from HIV-1 subtype B-infected subjects was used in the neutralization assays to test escape from neutralization by the sequential viruses from the four HIV-1 subtype B-infected subjects. The 10 plasma samples were obtained from HIV-1 treatment-naive, asymptomatic, chronically infected individuals attending the Veterans Affairs New York Harbor Healthcare Systems, New York.…”

Section: Study Subjects and Virus Isolationmentioning

confidence: 99%

“…Neutralization assays were performed in GHOST cells as previously described. 14,15 Briefly, equal volumes of patient-derived virus, at a dilution predetermined in earlier experiments to yield 200-1000 infected cells per 15,000-20,000 cells, and heat-inactivated patient's plasma or sera, at a final dilution of 1:40, were incubated for 1 h at 37°C. (We choose to use plasma at dilutions of 1/40 for all our experiments to avoid nonspecific neutralization and background noise at much lower dilutions and based on our prior experiments, the neutralization assays were best reproducible even with neutralizations Ͻ50%.)…”

Section: Ghost Cell Neutralization Assaymentioning

confidence: 99%

Neutralization Patterns and Evolution of Sequential HIV Type 1 Envelope Sequences in HIV Type 1 Subtype B-Infected Drug-Naive Individuals

Nyambi

Burda²,

Urbanski³

et al. 2008

AIDS Research and Human Retroviruses

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To design a vaccine that will remain potent against HIV-1, the immunogenic regions in the viral envelope that tend to change as well as those that remain constant over time must be identified. To determine the neutralization profiles of sequential viruses over time and study whether neutralization patterns correlate with sequence evolution, 12 broadly neutralizing plasmas from HIV-1 subtype B-infected individuals were tested for their ability to neutralize sequential primary HIV-1 subtype B viruses from four individuals. Three patterns of neutralization were observed, including a loss of neutralization sensitivity by viruses over time, an increase in neutralization sensitivity by sequential viruses, or a similarity in the sensitivity of sequential viruses to neutralization. Seven to 11 gp160 clones from each sequential virus sample were sequenced and analyzed to identify mutational patterns. Analysis of the envelope sequences of the sequential viruses revealed changes characteristic of the neutralization patterns. Viruses that evolved to become resistant to neutralizing antibodies also evolved with diverse sequences, with most of the changes being due to nonsynonymous mutations occurring in the V1/V2, as well as in the constant regions (C2, C3, C4), the most changes occurring in the C3. Viruses from the patient that evolved to become more sensitive to neutralization exhibited less sequence diversity with fewer nonsynonymous changes that occurred mainly in the V1/V2 region. The V3 region remained constant over time for all the viruses tested. This study demonstrates that as viruses evolve in their host, they either become sensitive or resistant to neutralization by antibodies in heterologous plasma and mutations in different envelope regions account for these changes in their neutralization profiles.

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“…This neutralising antibody response is initially restricted to autologous virus but gradually broadens, as the virus diversifies and the immune response follows in pursuit [2,30,33,47,64]. Broadly neutralising antibodies, which are able to neutralise a wide spectrum of primary isolates, appear years after primary infection, if at all.…”

Section: Lessons From Human Seramentioning

confidence: 98%

Clade Specific Neutralising Vaccines for HIV: An Appropriate Target?

Aasa-Chapman¹

2007

CHR

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The enormous diversity of the human immunodeficiency virus (HIV) has led to the idea that designing vaccines to specific geographic regions, or clades, could simplify the complexity of the task. Yet, despite the sequence diversity, all HIV viruses known to date interact with the same cellular receptors (CD4 and/or a coreceptor, CCR5 or CXCR4). In this review we examine the existing evidence to support a clade-specific vaccine strategy for induction of neutralising antibodies. We concentrate on lessons learnt from natural infection of humans. In short, the vast majority of studies to date indicate that neutralisation of HIV-1 is not clade specific. Potent sera tend to neutralise a range of heterologous viruses with no apparent clade preference, and none of the human neutralising monoclonal antibodies so far generated demonstrate significant clade preference. All but one of the most broadly neutralising antibodies are to functional regions involved in receptor interactions and plasma membrane fusion. Given these facts, we suggest that vaccine approaches that focus on 'clade-specific' and 'clade-generic' vaccines will logically converge on the same functionally conserved envelope structures. It still remains to be determined whether or not the task of designing a 'clade-generic' vaccine could be simplified by focusing on the viral envelopes with 'transmitting phenotypes'.

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Neutralizing antibody patterns and viral escape in HIV-1 non-B subtype chronically infected treatment-naive individuals

Cited by 8 publications

References 7 publications

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

Neutralization Patterns and Evolution of Sequential HIV Type 1 Envelope Sequences in HIV Type 1 Subtype B-Infected Drug-Naive Individuals

Clade Specific Neutralising Vaccines for HIV: An Appropriate Target?

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