scholarly journals Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

1989 ◽  
Vol 170 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
I Berkower ◽  
G E Smith ◽  
C Giri ◽  
D Murphy
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Neutralizing Epitope ◽  
Vaccine Strategy ◽  
Disease Pathogenesis ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

scholarly journals Progress in the rational design of an AIDS vaccine

2011 ◽  
Vol 366 (1579) ◽  
pp. 2759-2765 ◽  
Author(s):  
Gary J. Nabel ◽  
Peter D. Kwong ◽  
John R. Mascola
Keyword(s):  
Structural Biology ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Computational Modelling ◽  
Effective Vaccine ◽  
Aids Vaccine ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) has a high degree of genetic and antigenic diversity that has impeded the development of an effective vaccine using traditional methods. We are attempting to develop an AIDS vaccine by employing strategies that include structural biology and computational modelling, in an effort to develop immunogens capable of eliciting neutralizing antibodies of the requisite breadth and potency against circulating strains of HIV-1.

scholarly journals A Little Help From the Follicles: Understanding the Germinal Center Response to Human Immunodeficiency Virus 1 Infection and Prophylactic Vaccines

2017 ◽  
Vol 10 ◽  
pp. 117955571769554 ◽  
Author(s):  
Ebony N Gary ◽  
Michele A Kutzler
Keyword(s):  
Human Immunodeficiency Virus ◽  
Germinal Center ◽  
Neutralizing Antibodies ◽  
People Living With Hiv ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Global Pandemic ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus 1 (HIV-1) is the causative agent of AIDS. There are currently more than 35 million people living with HIV infection worldwide, and more than 2 million new infections occur each year. The global pandemic caused by HIV-1 is the subject of numerous research projects, with the development of a prophylactic vaccine and a therapeutic cure being the ultimate goals. The classic paradigms of vaccinology have proven incapable of producing a viable vaccine due to the complexity of the virus’ replication cycle, its genetic diversity, and a lack of understanding of the immune correlates of protection. Here, we briefly discuss recent vaccine approaches and the immune correlates of protection from HIV-1 infection with a focus on the role of the germinal center as a reservoir of replication-competent virus and its role in the development of broadly neutralizing antibodies in response to vaccination.

DNA vaccines encoding human immunodeficiency virus–1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1153-1159 ◽  
Author(s):  
Arya Biragyn ◽  
Igor M. Belyakov ◽  
Yen-Hung Chow ◽  
Dimiter S. Dimitrov ◽  
Jay A. Berzofsky ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Lymphocyte ◽  
Peptide Sequence ◽  
Dna Encoding ◽  
Neutralizing Activity ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

DNA immunizations with glycoprotein 120 (gp120) of human immunodeficiency virus–1 (HIV-1) usually require boosting with protein or viral vaccines to achieve optimal efficacy. Here, we demonstrate for the first time that mice immunized with DNA encoding gp120 fused with proinflammatory chemoattractants of immature dendritic cells, such as β-defensin 2, monocyte chemoattractant protein–3 (MCP-3/CCL7) or macrophage-derived chemokine (MDC/CCL22), elicited anti-gp120 antibodies with high titers of virus-neutralizing activity. The immunogenicity was further augmented with the use of chemokine fusion constructs with gp140, gp120 linked to the extracellular domain of gp41 via a 14–amino acid spacer peptide sequence. This construct elicited antibodies with more effective neutralizing activity than corresponding constructs expressing gp120. Responses were dependent on physical linkage with chemokine moiety, as no immunity was detected following immunization of mice with DNA encoding a free mixture of chemokine and gp120. Although the route of immunization was inoculation into skin, both systemic and mucosal CD8+ cytolytic immune responses were elicited in mice immunized with DNA expressing MCP-3 or β-defensin 2 fusion constructs. In contrast, no cytotoxic T lymphocyte activity (CTL) was detected in mice immunized with DNA encoding gp120 either alone or as fusion with MDC. Therefore, the potential for broad application of this approach lies in the induction of mucosal CTL and neutralizing antibodies to HIV-1 envelope, both key requirements for prevention of viral transmission and clearance of pathogenic HIV from mucosal reservoirs.

scholarly journals APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus–1 infection

2011 ◽  
Vol 72 (3) ◽  
pp. 207-212 ◽  
Author(s):  
P.A. Gourraud ◽  
A. Karaouni ◽  
J.M. Woo ◽  
T. Schmidt ◽  
J.R. Oksenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Sequence ◽  
Sequence Diversity ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1365-1372 ◽  
Author(s):  
Stefania Mitola ◽  
Silvano Sozzani ◽  
Walter Luini ◽  
Luca Primo ◽  
Alessandro Borsatti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Monocyte Chemotaxis ◽  
Endothelial Growth Factor ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.

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