Antibodies from Rabbits Immunized with HIV-1 Clade B SOSIP Trimers Can Neutralize Multiple Clade B Viruses by Destabilizing the Envelope Glycoprotein.

The high viral diversity of HIV-1 is a formidable hurdle for the development of an HIV-1 vaccine. Elicitation of broadly neutralizing antibodies (bNAbs) would offer a solution, but so far immunization strategies have failed to efficiently elicit bNAbs. To overcome these obstacles, it is important to understand the immune responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens. To gain more insight, we characterized monoclonal antibodies (MAbs) isolated from rabbits immunized with Env SOSIP trimers based on the clade B isolate AMC008. Four rabbits that were immunized three times with AMC008 trimer developed robust autologous and sporadic low-titer heterologous neutralizing responses. Seventeen AMC008 trimer-reactive MAbs were isolated using antigen-specific single B-cell sorting. Four of these MAbs neutralized the autologous AMC008 virus and several other clade B viruses. When visualized by electron microscopy, the complex of the neutralizing MAbs with the AMC008 trimer showed binding to the gp41 subunit with unusual approach angles, and we observed that their neutralization ability depended on their capacity to induce Env trimer dissociation. Thus, AMC008 SOSIP trimer immunization induced clade B-neutralizing MAbs with unusual approach angles with neutralizing effects that involve trimer destabilization. Optimizing these responses might provide an avenue to the induction of trimer-dissociating bNAbs. IMPORTANCE Roughly 32 million people have died as a consequence of HIV-1 infection since the start of the epidemic, and 1.7 million people still get infected with HIV-1 annually. Therefore, a vaccine to prevent HIV-1 infection is urgently needed. Current HIV-1 immunogens are not able to elicit the broad immune responses needed to provide protection against the large variation of HIV-1 strains circulating globally. A better understanding of the humoral immune responses elicited by immunization with state-of-the-art HIV-1 immunogens should facilitate the design of improved HIV-1 vaccine candidates. We identified antibodies with the ability to neutralize multiple HIV-1 viruses by destabilization of the envelope glycoprotein. Their weak but consistent cross-neutralization ability indicates the potential of this epitope to elicit broad responses. The trimer-destabilizing effect of the neutralizing MAbs, combined with detailed characterization of the neutralization epitope, can be used to shape the next generation of HIV-1 immunogens to elicit improved humoral responses after vaccination.

Deconfounding the effects of dominance and social acceptance on self-esteem.

Three studies examined the independent effects of social acceptance and dominance on self-esteem. In Studies 1 and 2, participants received false feedback regarding their relative acceptance and dominance in a laboratory group, and state self-esteem was assessed. Results indicated that acceptance and dominance feedback had independent effects on self-esteem. Study 2 showed that these effects were not moderated by individual differences in participants' self-reported responsivity to being accepted versus dominant. In Study 3, participants completed multiple measures of perceived dominance, perceived acceptance, and trait self-esteem. Results showed that both perceived dominance and perceived acceptance accounted for unique variance in trait self-esteem, but that perceived acceptance consistently accounted for substantially more variance than perceived dominance. Also, trait self-esteem was related to the degree to which participants felt accepted by specific people in their lives, but not to the degree to which participants thought those individuals perceived them as dominant.

Social coping strategies associated with quality of life decrements among psoriasis patients.

BACKGROUND: Individuals with psoriasis often report significant psychological distress, physical disability, social strain and reduced quality of life. Little is known about how they cope with the illness. OBJECTIVE: The primary aim of this study is to determine whether patients' efforts to cope with psoriasis are associated with better or worse health-related quality of life (HRQL). METHODS: Focus groups identified seven commonly used coping strategies that were subsequently measured, along with HRQL and other variables, in a survey of 318 individuals with psoriasis. RESULTS: Results revealed: (i) that psoriasis is associated with decrements in all quality of life domains that were assessed, and (ii) that commonly used coping strategies such as telling others about psoriasis, covering the lesions and avoiding people were associated with greater decrements in HRQL after controlling for covariates; however, telling others that psoriasis is not contagious was associated with smaller HRQL decreases. CONCLUSIONS: How patients cope with the social aspects of psoriasis is associated with their quality of life.