Selected Grantee Publications
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- 5 results found
- nci
- Infectious Diseases
- Imaging
Administration of Anti-HIV-1 Broadly Neutralizing Monoclonal Antibodies With Increased Affinity to Fcγ Receptors During Acute SHIV AD8-EO Infection
Dias et al., Nature Communications. 2024.
https://www.nature.com/articles/s41467-024-51848-y
Anti-HIV broadly neutralizing antibodies (bNAbs) mediate virus neutralization and antiviral effector functions through Fab and Fc domains, respectively. This study investigated the efficacy of wild-type (WT) bNAbs and modified bNAbs with enhanced affinity for Fcγ receptors (S239D/I332E/A330L [DEL]) after acute simian-HIVAD8-EO (SHIVAD8-EO) infection in male and female rhesus macaques. The emergence of the virus in the plasma and lymph nodes occurred earlier in macaques given DEL bNAbs than in those given WT bNAbs. Overall, the administration of DEL bNAbs revealed higher levels of immune responses. The results suggest that bNAbs with an enhanced Fcγ receptor affinity offer a potential therapeutic strategy by targeting HIV more effectively during early infection stages. Supported by ORIP (P40OD028116), NCI, and NIAID.
First-in-Human ImmunoPET Imaging of COVID-19 Convalescent Patients Using Dynamic Total-Body PET and a CD8-Targeted Minibody
Omidvari et al., Science Advances. 2023.
https://pubmed.ncbi.nlm.nih.gov/36993568/
Developing noninvasive methods for in vivo quantification of T cell distribution and kinetics is important because most T cells reside in the tissue. Investigators presented the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell distribution in healthy individuals and COVID-19 patients. Kinetic modeling results aligned with the expected T cell trafficking effects. Tissue-to-blood ratios were consistent with modeled net influx rates and flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory. Supported by ORIP (S10OD018223) and NCI.
Molecular Insights Into Antibody-Mediated Protection Against the Prototypic Simian Immunodeficiency Virus
Zhao et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-32783-2
Most simian immunodeficiency virus (SIV) vaccines have focused on inducing T cell responses alone or in combination with non-neutralizing antibody responses. To date, studies investigating neutralizing antibody (nAb) responses to protect against SIV have been limited. In this study, researchers isolated 12 potent monoclonal nAbs from chronically infected rhesus macaques of both sexes and mapped their binding specificities on the envelope trimer structure. They further characterized the structures using cryogenic electron microscopy, mass spectrometry, and computational modeling. Their findings indicate that, in the case of humoral immunity, nAb activity is necessary and sufficient for protection against SIV challenge. This work provides structural insights for future vaccine design. Supported by ORIP (P51OD011106), NIAID, and NCI.
In Vitro and In Vivo Functions of SARS-CoV-2 Infection-Enhancing and Neutralizing Antibodies
Li et al., Cell. 2021.
https://doi.org/10.1016/j.cell.2021.06.021
Antibody-dependent enhancement of infection is a concern for clinical use of antibodies. Researchers isolated neutralizing antibodies against the receptor-binding domain (RBD) or N-terminal domain (NTD) of SARS-CoV-2 spike from COVID-19 patients. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific binding modes. RBD and NTD antibodies mediated both neutralization and infection enhancement in vitro. However, infusion of these antibodies into mice or macaques resulted in suppression of virus replication, demonstrating that antibody-enhanced infection in vitro does not necessarily predict enhanced infection in vivo. RBD-neutralizing antibodies having cross-reactivity against coronaviruses were protective against SARS-CoV-2, the most potent of which was DH1047. Supported by ORIP (P40OD012217, U42OD021458, S10OD018164), NIAID, NCI, NIGMS, and NIH Common Fund.
Neutralizing Antibody Vaccine for Pandemic and Pre-Emergent Coronaviruses
Saunders et al., Nature. 2021.
https://doi.org/10.1038/s41586-021-03594-0
SARS-CoV-2 is a new member of the betacoronavirus (beta-CoV) genus, which also includes two common mild beta-CoVs and the life-threatening SARS-CoV-1 and MERS-CoV. Vaccines that elicit protective immunity against SARS-CoV-2 and beta-CoVs that circulate in animals could prevent future pandemics. Researchers designed a novel 24-mer SARS-CoV-2 receptor binding domain-sortase A conjugated nanoparticle vaccine (RBD-scNP). Investigators demonstrated that the immunization of macaques with RBD-scNP, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV, and multiple SARS-CoV-2 variants of concern. This pioneering approach serves as a multimeric protein platform for the further development of generalized anti-beta-CoV vaccines. Supported by ORIP (U42OD021458), NIAID, and NCI.