Breadth of Neutralizing Antibody Response to Human Immunodeficiency Virus Type 1 Is Affected by Factors Early in Infection but Does Not Influence Disease Progression

Piantadosi, Anne; Panteleeff, Dana; Blish, Catherine A.; Baeten, Jared M.; Jaoko, Walter; McClelland, R. Scott; Overbaugh, Julie

doi:10.1128/jvi.01149-09

Cited by 159 publications

(233 citation statements)

References 40 publications

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“…This has been interpreted as an indication that persistent antigen stimulation is required to develop neutralization breadth (53)(54)(55). In stark contrast, our study subject developed BnAbs while controlling viremia, which suggests that acquisition of HIV-1 neutralization breadth may not always require chronic stimulation with high levels of HIV-1 viremia.…”

Section: Figurecontrasting

confidence: 48%

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1

Bonsignori¹,

Wiehe²,

Grimm³

et al. 2014

J. Clin. Invest.

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Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

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Section: Figurecontrasting

confidence: 48%

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1

Bonsignori¹,

Wiehe²,

Grimm³

et al. 2014

J. Clin. Invest.

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“…We and others have previously discussed that the duration of HIV infection is positively associated with the breadth of cross-neutralizing antibody responses [6,7,11,12]. Here we show that such anti-viral responses become detectable in the blood of these subjects, on average, at 2.5 years after infection.…”

Section: Discussionsupporting

confidence: 47%

“…In chronic HIV-1 infection the breadth of serum crossneutralizing antibody activities positively correlates with the levels of plasma viremia [6,7,11,12]. Here, we recorded a positive correlation (p = 0.0026; R = 0.3615) between the breadth of the earliest cross-neutralizing antibody responses in HIV+ plasmas and the levels of plasma viremia.…”

Section: Factors Associated With the Emergence Of Crossneutralizing Asupporting

confidence: 51%

“…These latter responses are the ones an effective vaccine should elicit [9]. Several studies indicated that the breadth of plasma cross-neutralizing antibody responses is positively associated with plasma viral load [6,7,10,11,12], but very little is known about the time course of these responses. A recent study by van Gils et al, using samples collected at 2 and 4 years following infection, indicated that a greater number of infected subjects displayed cross-neutralizing activities at 4 than at 2 years [12].…”

Section: Introductionmentioning

confidence: 99%

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141 Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1

Mikell

Sather

Kalams

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%-30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2-3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest crossneutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination.

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“…Most HIV-1-infected individuals mount an HIV-1-specific humoral immune response, but these antibodies are considered strain-specific, as neutralizing activity is assumed to be limited to the autologous virus strain. Indeed, the majority of HIV-1-infected individuals do not develop cross-clade neutralizing activity that is capable of neutralizing HIV-1 variants from different subtypes (Li et al, 2007;Piantadosi et al, 2009;Sather et al, 2009). However, cross-reactive neutralization of different HIV-1 variants of the same subtype has received only little attention.…”

Section: Discussionmentioning

confidence: 99%