Co ‐inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma
Summary
The introduction of immunotherapy with checkpoint receptor blockade has changed the treatment of advanced cancers, at times inducing prolonged remission. Nevertheless, the success rate of the approach is variable across patients and different tumor types, and treatment is often accompanied by severe immune‐related side effects, suggesting the importance of co‐inhibitory pathway for both prevention of autoimmunity and failure of tumor rejection. A better understanding of how to uncouple anti‐tumor activity from loss of self‐tolerance is necessary to increase the therapeutic efficacy of checkpoint immunothera...
Source: Immunological Reviews - March 3, 2017 Category: Allergy & Immunology Authors: Liliana E. Lucca, David A. Hafler Tags: INVITED REVIEW Source Type: research
Introduction to checkpoint inhibitors and cancer immunotherapy
(Source: Immunological Reviews)
Source: Immunological Reviews - March 3, 2017 Category: Allergy & Immunology Authors: Arlene H. Sharpe Tags: INTRODUCTION Source Type: research
Issue Information
(Source: Immunological Reviews)
Source: Immunological Reviews - February 28, 2017 Category: Allergy & Immunology Tags: Issue Information Source Type: research
Antibody gene transfer with adeno ‐associated viral vectors as a method for HIV prevention
Summary
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 pro...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Jacqueline M. Brady, David Baltimore, Alejandro B. Balazs Tags: INVITED REVIEW Source Type: research
HIV antibodies for treatment of HIV infection
Summary
The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half‐lives, and are being considered as partners for long‐acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antib...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: David M. Margolis, Richard A. Koup, Guido Ferrari Tags: INVITED REVIEW Source Type: research
Use of broadly neutralizing antibodies for HIV ‐1 prevention
Summary
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. In animal models, there is abu...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Amarendra Pegu, Ann J. Hessell, John R. Mascola, Nancy L. Haigwood Tags: INVITED REVIEW Source Type: research
Anti ‐retroviral antibody FcγR‐mediated effector functions
Summary
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 s...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Stylianos Bournazos, Jeffrey V. Ravetch Tags: INVITED REVIEW Source Type: research
Survivors Remorse: antibody ‐mediated protection against HIV‐1
Summary
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 ...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: George K. Lewis, Marzena Pazgier, Anthony L. DeVico Tags: INVITED REVIEW Source Type: research
Systems serology for evaluation of HIV vaccine trials
Summary
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. These candidate vaccines, despite employing disparate ...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Margaret E. Ackerman, Dan H. Barouch, Galit Alter Tags: INVITED REVIEW Source Type: research
Complex immune correlates of protection in HIV ‐1 vaccine efficacy trials
Summary
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 vaccin...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Georgia D. Tomaras, Stanley A. Plotkin Tags: INVITED REVIEW Source Type: research
Polyvalent vaccine approaches to combat HIV ‐1 diversity
Summary
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. ...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Bette Korber, Peter Hraber, Kshitij Wagh, Beatrice H. Hahn Tags: INVITED REVIEW Source Type: research
Ontogeny ‐based immunogens for the induction of V2‐directed HIV broadly neutralizing antibodies
Summary
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. V2‐apex bNAbs are derived from rare precursors with long anionic CDR H3s that are o...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Penny L. Moore, Jason Gorman, Nicole A. Doria ‐Rose, Lynn Morris Tags: INVITED REVIEW Source Type: research
Germline ‐targeting immunogens
Summary
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. Using these newest bN...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Leonidas Stamatatos, Marie Pancera, Andrew T. McGuire Tags: INVITED REVIEW Source Type: research
Evolution of B cell analysis and Env trimer redesign
Summary
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 vacc...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Gunilla B. Karlsson Hedestam, Javier Guenaga, Martin Corcoran, Richard T. Wyatt Tags: INVITED REVIEW Source Type: research
Native ‐like Env trimers as a platform for HIV‐1 vaccine design
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 t...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Rogier W. Sanders, John P. Moore Tags: INVITED REVIEW Source Type: research
