Publications by authors named "M Anthony Moody"

618 Publications

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Sci Rep 2021 Jul 14;11(1):14494. Epub 2021 Jul 14.

Department of Biomedical Engineering, Duke University, 101 Science Dr., Campus, Box 90281, Durham, NC, 27708, USA.

A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial-based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofiber-based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofibers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof-of-concept for a nanofiber vaccine platform generating broad, high binding antibody responses against the HIV-1 envelope glycoprotein.
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http://dx.doi.org/10.1038/s41598-021-93702-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280189PMC
July 2021

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

Cell 2021 Jun 18. Epub 2021 Jun 18.

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.
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http://dx.doi.org/10.1016/j.cell.2021.06.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232969PMC
June 2021

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

JCI Insight 2021 Jul 6. Epub 2021 Jul 6.

Department of Pediatrics, Division of Infectious Diseases, Duke University School of Medicine, Durham, United States of America.

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses likely contribute to protection from reinfection.
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http://dx.doi.org/10.1172/jci.insight.150909DOI Listing
July 2021

Structural and compositional analysis of (InGa)(AsSb)/GaAs/GaP Stranski-Krastanov quantum dots.

Light Sci Appl 2021 Jun 15;10(1):125. Epub 2021 Jun 15.

Department of Applied Physics, Eindhoven University of Technology, 5612 AZ, Eindhoven, The Netherlands.

We investigated metal-organic vapor phase epitaxy grown (InGa)(AsSb)/GaAs/GaP Stranski-Krastanov quantum dots (QDs) with potential applications in QD-Flash memories by cross-sectional scanning tunneling microscopy (X-STM) and atom probe tomography (APT). The combination of X-STM and APT is a very powerful approach to study semiconductor heterostructures with atomic resolution, which provides detailed structural and compositional information on the system. The rather small QDs are found to be of truncated pyramid shape with a very small top facet and occur in our sample with a very high density of ∼4 × 10 cm. APT experiments revealed that the QDs are GaAs rich with smaller amounts of In and Sb. Finite element (FE) simulations are performed using structural data from X-STM to calculate the lattice constant and the outward relaxation of the cleaved surface. The composition of the QDs is estimated by combining the results from X-STM and the FE simulations, yielding ∼InGaAsSb, where x = 0.25-0.30 and y = 0.10-0.15. Noticeably, the reported composition is in good agreement with the experimental results obtained by APT, previous optical, electrical, and theoretical analysis carried out on this material system. This confirms that the InGaSb and GaAs layers involved in the QD formation have strongly intermixed. A detailed analysis of the QD capping layer shows the segregation of Sb and In from the QD layer, where both APT and X-STM show that the Sb mainly resides outside the QDs proving that Sb has mainly acted as a surfactant during the dot formation. Our structural and compositional analysis provides a valuable insight into this novel QD system and a path for further growth optimization to improve the storage time of the QD-Flash memory devices.
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http://dx.doi.org/10.1038/s41377-021-00564-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203795PMC
June 2021

Functional Homology for Antibody-Dependent Phagocytosis Across Humans and Rhesus Macaques.

Front Immunol 2021 20;12:678511. Epub 2021 May 20.

Department of Surgery, Duke University School of Medicine, Durham, NC, United States.

Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate of reduced infection risk in multiple RM studies and the human HVTN505 trial. This recurrent finding suggests that antibody responses with the capability to mediate ADP are most likely a desirable component of vaccine responses aimed at protecting against HIV-1 acquisition. As use of RM models is essential for development of the next generation of candidate HIV-1 vaccines, there is a need to determine how effectively ADP activity observed in RMs translates to activity in humans. In this study we compared ADP activity of human and RM monocytes and polymorphonuclear leukocytes (PMN) to bridge this gap in knowledge. We observed considerable variability in the magnitude of monocyte and PMN ADP activity across individual humans and RM that was not dependent on FcR alleles, and only modestly impacted by cell-surface levels of FcRs. Importantly, we found that for both human and RM phagocytes, ADP activity of antibodies targeting the CD4 binding site was greatest when mediated by human IgG3, followed by RM and human IgG1. These results demonstrate that there is functional homology between antibody and FcRs from these two species for ADP. We also used novel RM IgG1 monoclonal antibodies engineered with elongated hinge regions to show that hinge elongation augments RM ADP activity. The RM IgGs with engineered hinge regions can achieve ADP activity comparable to that observed with human IgG3. These novel modified antibodies will have utility in passive immunization studies aimed at defining the role of IgG3 and ADP in protection from virus challenge or control of disease in RM models. Our results contribute to a better translation of human and macaque antibody and FcR biology, and may help to improve testing accuracy and evaluations of future active and passive prevention strategies.
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http://dx.doi.org/10.3389/fimmu.2021.678511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174565PMC
May 2021
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