Preclinical Immunogenicity and Efficacy of a Multiple Antigen-Presenting System (MAPSTM) SARS-CoV-2 Vaccine.

Despite the remarkable success of SARS-CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen-Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS-CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS-CoV-2 challenge. The SARS-CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS-CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine.

Evaluation of a pragmatic trial of a collaborative school-based obesity prevention intervention in a low-income urban district.

Broader adoption of effective school-based obesity prevention interventions is critical to the success of ongoing efforts to address the childhood obesity epidemic. School-level barriers to adopting evidence-based interventions may be overcome by empowering school-level leaders to select appropriate intervention components. We used a quasi-experimental pragmatic trial design to evaluate a tailored obesity prevention intervention in 9 schools in a mid-sized urban school district in upstate New York from fall 2013 to spring 2016. We analyzed repeated height and weight measurements from an existing district screening system on 5882 students from intervention and control schools matched using propensity score methods. We assessed diet and physical activity changes in intervention schools using surveys and direct observation. The intervention led to a change of -0.27 (p = 0.026, 95% Confidence Interval (CI): -0.51, -0.03) and -0.28 (p = 0.031, 95% CI: -0.54, -0.03) BMI units in spring 2014 and fall 2014, respectively. There were no significant differences between intervention and control from spring 2015 to spring 2016. Despite the lack of sustained effects on BMI, we demonstrated the potential of supporting school leaders in a low-income district to implement supportive policy and practice changes and of using an existing BMI screening system to reduce the burden of health promotion evaluation.

Crystal Structure of the Human Cytomegalovirus Glycoprotein B.

Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB), thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-Å resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.

Nonword repetition errors of children with and without specific language impairments (SLI).

BACKGROUND: Two ubiquitous findings from the literature are that (1) children with specific language impairments (SLI) repeat nonwords less accurately than peers with typical language development (TLD), and (2) all children repeat nonwords with frequent phonotactic patterns more accurately than low-probability nonwords. Many studies have examined repetition accuracy, but little work has examined children's errors. AIMS: To examine nonword repetition errors from a previously published study in terms of phonotactic probability. METHODS & PROCEDURES: Eighteen children with SLI (mean age = 9;2) and 18 age-matched controls (mean age = 8;11) repeated three- and four-syllable nonwords. Substitutions were analysed in terms of phoneme frequency and phonotactic probability of the syllable containing the substitution. OUTCOMES & RESULTS: Results for all children show that phoneme substitutions generally involved replacement with more frequently occurring phonemes. Also, the resulting phonotactic probability within syllables containing substitutions was greater than the probability of the targets. This trend did not differ by group. CONCLUSIONS & IMPLICATIONS: These results suggest that both children with SLI and children with TLD substitute less frequent phonemes with more frequent ones, and less probabilistic syllables with higher probability ones.