Neutralizing antibodies to HIV-1 induced by immunization

McCoy, Laura E.; Weiss, Robin A.

doi:10.1084/jem.20121827

Cited by 135 publications

(127 citation statements)

References 170 publications

(253 reference statements)

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“…Until recently, very few immunization studies had induced even Tier‐2 autologous neutralization, let alone a broad response 90, 91, 92, 93. Post‐immune neutralization titers are lower than those seen in elite neutralizer bnAb donors, thus neutralizing Abs may be less frequent among the post‐immunization B‐cell population.…”

Section: Discussionmentioning

confidence: 99%

Identification and specificity of broadly neutralizing antibodies against HIV

McCoy

Burton

2017

Immunological Reviews

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207

193

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SummaryBeginning in 2009, studies of the humoral responses of HIV‐positive individuals have led to the identification of scores, if not hundreds, of antibodies that are both broadly reactive and potently neutralizing. This development has provided renewed impetus toward an HIV vaccine and led directly to the development of novel immunogens. Advances in identification of donors with the most potent and broad anti‐HIV serum neutralizing responses were crucial in this effort. Equally, development of methods for the rapid generation of human antibodies from these donors was pivotal. Primarily these methods comprise single B‐cell culture coupled to high‐throughput neutralization screening and flow cytometry‐based sorting of single B cells using HIV envelope protein baits. In this review, the advantages and disadvantages of these methodologies are discussed in the context of the specificities targeted by individual antibodies and the need for further improvements to evaluate HIV vaccine candidates.

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Section: Discussionmentioning

confidence: 99%

Identification and specificity of broadly neutralizing antibodies against HIV

McCoy

Burton

2017

Immunological Reviews

Self Cite

207

193

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“…Because gp120 (20)(21)(22)(23)(24) as well as anti-gp120 Abs (74)(75)(76) are present in HIV-1 patients, gp120-anti-gp120 ICs are likely to be generated and abundant in vivo (54,55). We therefore generated such gp120-anti-gp120 ICs by coincubating recombinant gp120 with two different human IgG anti-gp120 mAb at a molar gp120/ anti-gp120 mAb ratio of ∼4:5.…”

Section: Gp120-anti-gp120 Ics Activate Cd4 + T Cells In a Comparable mentioning

confidence: 99%

The Orientation of HIV-1 gp120 Binding to the CD4 Receptor Differentially Modulates CD4+ T Cell Activation

Zimmermann

Liechti

Haas

et al. 2015

The Journal of Immunology

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Progressive quantitative and qualitative decline of CD4+ T cell responses is one hallmark of HIV-1 infection and likely depends on several factors, including a possible contribution by the HIV-1 envelope glycoprotein gp120, which binds with high affinity to the CD4 receptor. Besides virion-associated and cell-expressed gp120, considerable amounts of soluble gp120 are found in plasma or lymphoid tissue, predominantly in the form of gp120–anti-gp120 immune complexes (ICs). Because the functional consequences of gp120 binding to CD4+ T cells are controversially discussed, we investigated how gp120 affects TCR-mediated activation of human CD4+ T cells by agonistic anti-CD3 mAb or by HLA class II–presented peptide Ags. We show that the spatial orientation of gp120–CD4 receptor binding relative to the site of TCR engagement differentially affects TCR signaling efficiency and hence CD4+ T cell activation. Whereas spatially and temporally linked CD4 and TCR triggering at a defined site promotes CD4+ T cell activation by exceeding local thresholds for signaling propagation, CD4 receptor engagement by gp120-containing ICs all around the CD4+ T cell undermine its capacity in supporting proximal TCR signaling. In vitro, gp120 ICs are efficiently captured by CD4+ T cells and thereby render them hyporesponsive to TCR stimulation. Consistent with these in vitro results we show that CD4+ T cells isolated from HIV+ individuals are covered with ICs, which at least partially contain gp120, and suggest that IC binding to CD4 receptors might contribute to the progressive decline of CD4+ T cell function during HIV-1 infection.

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“…[7][8][9] Since no candidate immunogen is capable of stimulating broadly neutralizing antibodies, a protective vaccine against HIV-1 infection based solely on the elicitation of protective antibodies is still not viable. 10,11 While non-neutralizing antibodies may effectively protect against HIV-1 infection, correlates of protection have still not been defined. 12 A vaccine that induces HIV-1 specific T cell responses is, therefore, an important alternative to vaccines that stimulate broadly neutralizing antibodies.…”

Section: Introductionmentioning

confidence: 99%