Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine.

Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc.

Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

Smallpox (variola virus) is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans.

Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries characterized by leukocyte accumulation in the vessel wall. Both innate and adaptive immune responses contribute to atherogenesis, but the identity of atherosclerosis-relevant antigens and the role of antigen presentation in this disease remain poorly characterized. We developed live-cell imaging of explanted aortas to compare the behavior and role of APCs in normal and atherosclerotic mice.

Protective murine and human monoclonal antibodies against eczema vaccinatum.

Background: Eczema vaccinatum is the most common severe pathology associated with smallpox vaccination (vaccinia virus), occurring at high rates among individuals with a previous history of atopic dermatitis (atopic eczema).

Methods: Monoclonal antibodies capable of neutralizing vaccinia virus, anti-H3 and anti-B5, were developed as a potential therapy for treatment of human eczema vaccinatum.

Results: Using a small animal model of eczema vaccinatum, we demonstrated that both murine and fully human monoclonal antibodies effectively limited eczema vaccinatum disease, foreshortening both the disease kinetics and the severity of the erosive viral skin lesions.

Protection against or triggering of Type 1 diabetes? Different roles for viral infections.

The emergence of autoreactivity that ultimately destroys insulin-producing β-cells and causes Type 1 diabetes (T1D) is a result of genetic susceptibility and environmental factors, such as viral infections. The ability to induce strong cellular immune responses and to cause inflammation in the target organ makes viral infections prime candidates for the initiation of islet autoreactivity. Indeed, certain viruses have been linked to the occurrence of T1D based on epidemiological, serological and histological findings; and several rodent studies clearly demonstrate that viral infections can trigger autoimmunity.

Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.

Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice.

Selective CD4+ T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities.

Antibody responses are critical components of protective immune responses to many pathogens, but parameters determining which proteins are targeted remain unclear. Vaccination with individual MHC-II-restricted vaccinia virus (VACV, smallpox vaccine) epitopes revealed that CD4(+) T cell help to B cells was surprisingly nontransferable to other virion protein specificities. Many VACV CD4(+) T cell responses identified in an unbiased screen targeted antibody virion protein targets, consistent with deterministic linkage between specificities.