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Immunological Reviews

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https://www.readbyqxmd.com/read/28133814/identification-and-specificity-of-broadly-neutralizing-antibodies-against-hiv
#1
REVIEW
Laura E McCoy, Dennis R Burton
Beginning 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...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133813/the-hiv-1-envelope-glycoprotein-structure-nailing-down-a-moving-target
#2
REVIEW
Andrew B Ward, Ian A Wilson
Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133812/antibodyomics-bioinformatics-technologies-for-understanding-b-cell-immunity-to-hiv-1
#3
REVIEW
Peter D Kwong, Gwo-Yu Chuang, Brandon J DeKosky, Tatyana Gindin, Ivelin S Georgiev, Thomas Lemmin, Chaim A Schramm, Zizhang Sheng, Cinque Soto, An-Suei Yang, John R Mascola, Lawrence Shapiro
Numerous antibodies have been identified from HIV-1-infected donors that neutralize diverse strains of HIV-1. These antibodies may provide the basis for a B cell-mediated HIV-1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics-based approach to understand the genetic and immunologic processes controlling the development of HIV-1-neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next-generation sequencing of B-cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6)...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133811/complex-immune-correlates-of-protection-in-hiv-1-vaccine-efficacy-trials
#4
REVIEW
Georgia D Tomaras, Stanley A Plotkin
Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine-mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identification of specific immune responses responsible for pathogen protection enables vaccine development and provides insights into host defenses against pathogens and the immunological mechanisms that most effectively fight infection. Defining immunological correlates of transmission risk in preclinical and clinical HIV-1 vaccine trials has moved the HIV-1 vaccine development field forward and directed new candidate vaccine development...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133810/systems-serology-for-evaluation-of-hiv-vaccine-trials
#5
REVIEW
Margaret E Ackerman, Dan H Barouch, Galit Alter
The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133809/survivors-remorse-antibody-mediated-protection-against-hiv-1
#6
REVIEW
George K Lewis, Marzena Pazgier, Anthony L DeVico
It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133808/antibody-gene-transfer-with-adeno-associated-viral-vectors-as-a-method-for-hiv-prevention
#7
REVIEW
Jacqueline M Brady, David Baltimore, Alejandro B Balazs
Broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) show great promise in HIV prevention as they are capable of potently neutralizing a considerable breadth of genetically diverse strains. Passive transfer of monoclonal bNAb proteins can confer protection in animal models of HIV infection at modest concentrations, inspiring efforts to develop an HIV vaccine capable of eliciting bNAb responses. However, these antibodies demonstrate high degrees of somatic mutation and other unique characteristics that may hinder the ability of conventional approaches to consistently and effectively produce bNAb analogs...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133807/host-controls-of-hiv-broadly-neutralizing-antibody-development
#8
REVIEW
Garnett Kelsoe, Barton F Haynes
Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti-tumor CD8 T-cell responses in the treatment of certain malignancies...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133806/native-like-env-trimers-as-a-platform-for-hiv-1-vaccine-design
#9
REVIEW
Rogier W Sanders, John P Moore
We describe the development and potential use of various designs of recombinant HIV-1 envelope glycoprotein trimers that mimic the structure of the virion-associated spike, which is the target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV-1 strains. Among the topics we address are the designs of various constructs; how native-like trimers can be produced and purified; the properties of such trimers in vitro and their immunogenicity in various animals; and the immunization strategies that may lead to the eventual elicitation of broadly neutralizing antibodies...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133805/evolution-of-b-cell-analysis-and-env-trimer-redesign
#10
REVIEW
Gunilla B Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T Wyatt
HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133804/immunologic-characteristics-of-hiv-infected-individuals-who-make-broadly-neutralizing-antibodies
#11
REVIEW
Persephone Borrow, M Anthony Moody
Induction 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...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133803/use-of-broadly-neutralizing-antibodies-for-hiv-1-prevention
#12
REVIEW
Amarendra Pegu, Ann J Hessell, John R Mascola, Nancy L Haigwood
Antibodies have a long history in antiviral therapy, but until recently, they have not been actively pursued for HIV-1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV-1 isolates have reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV-1...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133802/antibody-virus-co-evolution-in-hiv-infection-paths-for-hiv-vaccine-development
#13
REVIEW
Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B Williams, S Munir Alam, David C Montefiori, Barton F Haynes
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...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133801/anti-retroviral-antibody-fc%C3%AE-r-mediated-effector-functions
#14
REVIEW
Stylianos Bournazos, Jeffrey V Ravetch
The antiviral activity of antibodies reflects the bifunctional properties of these molecules. While the Fab domains mediate highly specific antigenic recognition to block virus entry, the Fc domain interacts with diverse types of Fcγ receptors (FcγRs) expressed on the surface of effector leukocytes to induce the activation of distinct immunomodulatory pathways. Fc-FcγR interactions are tightly regulated to control IgG-mediated inflammation and immunity and are largely determined by the structural heterogeneity of the IgG Fc domain, stemming from differences in the primary amino acid sequence of the various subclasses, as well as the structure and composition of the Fc-associated N-linked glycan...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133800/polyvalent-vaccine-approaches-to-combat-hiv-1-diversity
#15
REVIEW
Bette Korber, Peter Hraber, Kshitij Wagh, Beatrice H Hahn
A key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversity, and outline the rationale behind several polyvalent vaccine design strategies that are currently under evaluation. Vaccine-elicited T-cell responses, which contribute to the control of HIV-1 in natural infections, are currently being considered in both prevention and treatment settings...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133799/human-ig-knockin-mice-to-study-the-development-and-regulation-of-hiv-1-broadly-neutralizing-antibodies
#16
REVIEW
Laurent Verkoczy, Frederick W Alt, Ming Tian
A major challenge for HIV-1 vaccine research is developing a successful immunization approach for inducing broadly neutralizing antibodies (bnAbs). A key shortcoming in meeting this challenge has been the lack of animal models capable of identifying impediments limiting bnAb induction and ranking vaccine strategies for their ability to promote bnAb development. Since 2010, immunoglobulin knockin (KI) technology, involving inserting functional rearranged human variable exons into the mouse IgH and IgL loci has been used to express bnAbs in mice...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133798/tfh-cells-and-hiv-bnabs-an-immunodominance-model-of-the-hiv-neutralizing-antibody-generation-problem
#17
REVIEW
Colin Havenar-Daughton, Jeong Hyun Lee, Shane Crotty
The generation of HIV bnAbs may be one of the greatest feats of the human immune system and our best hope of finally creating an HIV vaccine. The striking amount of somatic hypermutation in HIV bnAbs led to the hypothesis that T follicular helper (Tfh) cells and germinal centers (GC) play a critical role in the ability of the immune system to generate these uncommon antibodies. In this review, we first summarize what is known about the immunological process of HIV bnAb development, the challenges of eliciting bnAbs via immunizations, and the putative central roles of Tfh cells and GC in the generation of HIV bnAbs...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133797/ontogeny-based-immunogens-for-the-induction-of-v2-directed-hiv-broadly-neutralizing-antibodies
#18
REVIEW
Penny L Moore, Jason Gorman, Nicole A Doria-Rose, Lynn Morris
The development of a preventative HIV vaccine able to elicit broadly neutralizing antibodies (bNAbs) remains a major challenge. Antibodies that recognize the V2 region at the apex of the HIV envelope trimer are among the most common bNAb specificities during chronic infection and many exhibit remarkable breadth and potency. Understanding the developmental pathway of these antibodies has provided insights into their precursors, and the viral strains that engage them, as well as defined how such antibodies mature to acquire breadth...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133796/germline-targeting-immunogens
#19
REVIEW
Leonidas Stamatatos, Marie Pancera, Andrew T McGuire
In 2009, Dimitrov's group reported that the inferred germline (iGL) forms of several HIV-1 broadly neutralizing antibodies (bNAbs) did not display measurable binding to a recombinant gp140 Env protein (derived from the dual-tropic 89.6 virus), which was efficiently recognized by the mature (somatically mutated) antibodies. At that time, a small number of bNAbs were available, but in the following years, the implementation of high-throughput B-cell isolation and sequencing assays and of screening methodologies facilitated the isolation of greater numbers of bNAbs from infected subjects...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133795/the-quest-for-an-antibody-based-hiv-vaccine
#20
Barton F Haynes, John R Mascola
No abstract text is available yet for this article.
January 2017: Immunological Reviews
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