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Summary The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally., Graphical Abstract, Highlights • The Gn glycoprotein of Rift Valley fever virus elicits potent neutralizing antibodies • Derived a class of monoclonal antibodies that protects in an animal model • A distinct region on RVFV Gn constitutes a key site of vulnerability • Antibodies are predicted to prevent exposure of viral fusion loops, Allen et al. reveal a molecular basis of antibody-mediated neutralization of Rift Valley fever virus, an important human and animal pathogen. They isolate and demonstrate the protective efficacy of a monoclonal antibody in a murine model of virus infection, providing a blueprint for rational therapeutic and vaccine design.

Calls for new ways to teach science include an emphasis on the human endeavor of science and for making science more relevant to a feminine perspective. This quasi-experimental intervention study of 166 middle school students approaches the teaching of the nature of science in an explicit and reflective way that also enhances the humanistic perspective of scientific knowledge construction. Girls in the experimental group significantly outperformed both boys in the experimental group and boys and girls in the comparison group on nature of science knowledge and on content knowledge. Differences were also found in the qualitative results. Girls saw the process of cognition as a group endeavor, whereas boys reported the process as being generated by themselves, with guidance from books or from the teacher. Additionally, girls in the experimental group tended to rely more on evidence in making conclusions and boys relied more on authority when they developed the "big ideas" in their inquiry., Advancing Women in Leadership Journal, Vol. 30 (2010)

This research examined the gender typing of managerial subroles for entry, middle and senior-level positions to evaluate if gender typing serves as a barrier to women's advancement into senior level positions. Interscholastic athletic directors and managers in the sport industry (n = 167) evaluated the importance of 19 managerial subroles for entry, middle, and senior level managers. Results indicate feminine managerial subroles were more important for entry and middle level managers than masculine managerial subroles (p < .05). There was no significant difference between masculine and feminine subroles in senior level manager positions. Feminine subroles may be more important than masculine subroles for entry and middle level positions while both feminine and masculine subroles are important for senior level managers., Advancing Women in Leadership Journal, Vol. 30 (2010)

Understanding the antibody response in HIV-1 infection is important to vaccine design. We have studied the antibody response to HIV-1 envelope at the molecular level and determined the characteristics of neutralizing and non-neutralizing antibodies. These antibodies were isolated from phage display libraries prepared from long-term seropositive asymptomatic individuals. The HIV-1 envelope is presented to the immune system in several antigenically distinct configurations: unprocessed gp160, gp120 and gp41 subunits and native envelope, each of which may be important in eliciting an antibody response in HIV-1 infection. The antibodies tested characteristically had poor affinities for native envelope as expressed on the surface of virions or infected cells, but had high affinities against non-native forms of HIV-1 envelope (viral debris). An exceptionally potent neutralizing antibody in contrast, bound native envelope with equivalent or somewhat higher affinity than this. This indicates that the antibody response in HIV-1 infection is principally elicited by viral debris rather than virions, and that these antibodies bind and neutralize viruses sub-optimally. Potential vaccines should be designed to elicit responses against native envelope.

Background Broadly neutralizing antibodies (bnAbs) directed against the mannose-patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the 323IGDIR327 motif of the V3 loop. We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. Results Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. Conclusions These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. Electronic supplementary material The online version of this article (doi:10.1186/s12977-016-0241-5) contains supplementary material, which is available to authorized users.

Maternal HIV-1-specific antibodies are efficiently transferred to newborns, but their role in disease control is unknown. We administered neutralizing IgG, including the human neutralizing monoclonal IgG1b12, at levels insufficient to block infection, to six newborn macaques before oral challenge with simian-HIV strain SF162P3 (SHIVSF162P3). All of the macaques rapidly developed neutralizing antibodies and had significantly reduced plasma viremia for six months. These studies support the use of neutralizing antibodies in enhancing B cell responses and viral control in perinatal settings. © 2010 Nature America, Inc. All rights reserved.