Antibody neutralization and escape by HIV-1

Wei, Xiping; Decker, Julie M.; Wang, Shuyi; Hui, Huxiong; Kappes, John C.; Wu, Xiaoyun; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Kilby, J. Michael; Saag, Michael S.; Komarova, Natalia L.; Nowak, Martin A.; Hahn, Beatrice H.; Kwong, Peter D.; Shaw, George M.

doi:10.1038/nature01470

Cited by 2,209 publications

(2,425 citation statements)

References 25 publications

Supporting

Mentioning

2,282

Contrasting

Unclassified

Order By: Relevance

“…Very few bnAbs were known prior to this time (e.g., b12, 2G12, 2F5, 4E10), and the breadth and potency of these early bnAbs pale in comparison to the newer bnAbs (12). High throughput assay technologies with molecularly cloned Env-pseudotyped viruses (67–69), combined with a heightened awareness of the importance of the “Tier 2” neutralization phenotype of most circulating strains (70, 71) were major contributors. New reporter gene assays in either TZM-bl or U87.CD4.CCR5.CXCR4 became available that are more rapid, sensitive and less costly than other assays, and are amenable to high standards of optimization and validation (72).…”

Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

“…High fidelity functional Env clones of the TF virus and later variants obtained by single genome amplification (SGA) have been used to demonstrate multiple rounds of autologous neutralization and escape over the course of infection (67). In most cases contemporaneous serum at each stage of escape is capable of neutralizing earlier but not later autologous Env variants (67, 84). Finally, as mentioned above, it is noteworthy that the UCA of most bnAb lineages exhibited little or no neutralizing activity against the autologous Tier 2 T/F virus.…”

Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Bonsignori

Liao

Gao

et al. 2017

Immunological Reviews

162

150

View full text Add to dashboard Cite

Summary Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the viral and immunologic events that occur during HIV-1 infection, and then to mimic those events with a vaccine formulation. This concept has led to efforts to map both virus and antibody events that occur from the time of HIV-1 transmission to development of bnAbs. This work has revealed that a virus-antibody “arms race” occurs in which a HIV-1 transmitted/founder (TF) Env induces autologous neutralizing antibodies that can not only neutralize the TF virus but also can select virus escape mutants that in turn select affinity-matured neutralizing antibodies. From these studies has come a picture of bnAb development that has led to new insights in host-pathogen interactions and, as well, led to insight into immunologic mechanisms of control of bnAb development. Here we review the progress to date in elucidating bnAb B cell lineages in HIV-1 infection, discuss new research leading to understanding the immunologic mechanisms of bnAb induction, and address issues relevant to the use of this information for the design of new HIV-1 sequential envelope vaccine candidates.

show abstract

Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Bonsignori

Liao

Gao

et al. 2017

Immunological Reviews

162

150

View full text Add to dashboard Cite

show abstract

“…The development of antibody responses follows a pattern, with antiviral antibodies being detected first as immune complexes41 followed by free antibody directed at the HIV‐1 envelope (Env) glycoprotein 41 (gp41) subunit,41, 42 and then by the development of Env glycoprotein 120 (gp120)‐binding antibodies 41. These early antibody responses do not neutralize or place selective pressure on virus evolution41; antibodies capable of neutralizing autologous viruses are not detectable until weeks to months after infection is established19, 20 and have little to no activity against heterologous HIV‐1 strains 43. The initial gp41‐directed antibody response is polyreactive and the antibodies are highly mutated,42 and evidence indicates that at least some early responding B cells are primed prior to infection by non‐HIV‐1 antigens such as proteins contained in intestinal microbiota 44…”

Section: Development Of Broadly Neutralizing Antibodies In Hiv‐1 Infementioning

confidence: 99%

“…Neutralization has been shown to exert immune pressure on HIV‐1,19, 20 while the role of other antibody‐mediated functions in exerting immune pressure is unclear, primarily because antibodies that mediate ADCC and other activities often also neutralize 21. Regardless, multiple studies have demonstrated that virus neutralization is a driver of both virus and antibody diversity,22, 23, 24, 25, 26 although neutralization of autologous viruses does not always cause the extinction of susceptible virus populations in an infected individual 25…”

Section: Introductionmentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

View full text Add to dashboard Cite

SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

show abstract

“…This was assayed by performing single-cycle infection experiments using the TZM-bl luciferase reporter gene assay system. 12 This cell line is engineered to express high levels of CCR5 and CD4 and contains a luciferase reporter gene under control of the HIV-1 promoter, which is inducible in trans by the viral protein Tat. 13 TZM-bl cells were infected with JR-CSF in the presence or absence of the test compounds.…”

mentioning

confidence: 99%

Inhibition of HIV Fusion with Multivalent Gold Nanoparticles

et al. 2008

View full text Add to dashboard Cite

The design and synthesis of a multivalent gold nanoparticle therapeutic is presented. SDC-1721, a fragment of the potent HIV inhibitor TAK-779, was synthesized and conjugated to 2.0 nm diameter gold nanoparticles. Free SDC-1721 had no inhibitory effect on HIV infection; however, the (SDC-1721)-gold nanoparticle conjugates displayed activity comparable to that of TAK-779. This result suggests that multivalent presentation of small molecules on gold nanoparticle surfaces can convert inactive drugs into potent therapeutics.

show abstract

Antibody neutralization and escape by HIV-1

Cited by 2,209 publications

References 25 publications

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Inhibition of HIV Fusion with Multivalent Gold Nanoparticles

Contact Info

Product

Resources

About