Publications by authors named "Gina C Donofrio"
Article Synopsis
- The emergence of SARS-CoV-2 variants with reduced vaccine effectiveness shows the need for new vaccine designs that provide wider protection.
- This study evaluates the antibody response from a novel vaccine, the Spike Ferritin Nanoparticle (SpFN), in non-human primates, particularly focusing on the antibodies that target different regions of the virus's Spike protein.
- Six potent neutralizing antibodies were identified, demonstrating broad effectiveness against various sarbecovirus variants, including Delta and Omicron, with one antibody showing strong protection in murine studies.
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site.
View Article and Find Full Text PDFEliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort.
View Article and Find Full Text PDFArticle Synopsis
- Researchers are investigating therapeutic monoclonal antibodies (mAbs) targeting different vulnerable sites on the SARS-CoV-2 spike protein to prevent the virus from escaping treatment and to enhance protection against variants.
- They discovered several effective neutralizing antibodies that can be used in combination, showing strong protection in a mouse model of infection.
- One specific RBD antibody, WRAIR-2125, was particularly effective against all major variants and, when used with other mAbs, helped prevent the virus from evading the immune response.
Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14-43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia.
View Article and Find Full Text PDFAb-dependent enhancement (ADE) of dengue virus (DENV) infection is mediated through the interaction of viral immune complexes with FcγRs, with notable efficiency of FcγRII. Most human dengue target cells coexpress activating (FcγRIIa) and inhibitory (FcγRIIb) isoforms, but their relative roles in ADE are not well understood. We studied the effects of FcγRIIa and FcγRIIb by transfecting cells to express each individual receptor isoform or through coexpression of both isoforms.
View Article and Find Full Text PDFAntibody-dependent enhancement (ADE) is implicated in severe, usually secondary, dengue virus (DV) infections. Preexisting heterotypic antibodies, via their Fc-gamma receptor (FcγR) interactions, may increase disease severity through enhanced target cell infection. Greater numbers of infected target cells may contribute to higher viremia and excess cytokine levels often observed in severe disease.
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