Antibody ‐virus co‐evolution in HIV infection: paths for HIV vaccine development
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 transmit...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Mattia Bonsignori, Hua ‐Xin Liao, Feng Gao, Wilton B. Williams, S. Munir Alam, David C. Montefiori, Barton F. Haynes Tags: INVITED REVIEW Source Type: research
Genetic and structural analyses of affinity maturation in the humoral response to HIV ‐1
Summary
Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV‐1 infection are extraordinarily mutated. One goal of HIV‐1 vaccine development is to induce antibodies that are similar to the most potent and broad BNAbs isolated from infected subjects. The most effective BNAbs have very high mutation frequencies, indicative of the long periods of continual activation necessary to acquire the BNAb phenotype through affinity maturation. Understanding the mutational patterns that define the maturation pathways in BNAb development is critical to vaccine design efforts to recapitulate through vaccination the...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Thomas B. Kepler, Kevin Wiehe Tags: INVITED REVIEW Source Type: research
Antibodyomics: bioinformatics technologies for understanding B ‐cell immunity to HIV‐1
Summary
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 tra...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: 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 Tags: INVITED REVIEW Source Type: research
Human Ig knockin mice to study the development and regulation of HIV ‐1 broadly neutralizing antibodies
Summary
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. This approach has allowed immune tolerance mechanisms limiting bnAb p...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Laurent Verkoczy, Frederick W. Alt, Ming Tian Tags: INVITED REVIEW Source Type: research
Host controls of HIV broadly neutralizing antibody development
Summary
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 treat...
Source: Immunological Reviews - January 29, 2017 Category: Allergy & Immunology Authors: Garnett Kelsoe, Barton F. Haynes Tags: INVITED REVIEW Source Type: research
