Selected Grantee Publications
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- 191 results found
- COVID-19/Coronavirus
- HIV/AIDS
A Single-Dose Intranasal Live-Attenuated Codon Deoptimized Vaccine Provides Broad Protection Against SARS-CoV-2 and Its Variants
Liu et al., Nature Communications. 2024.
https://pubmed.ncbi.nlm.nih.gov/39187479
Researchers developed an intranasal, single-dose, live-attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccine (CDO-7N-1) using codon deoptimization. This vaccine demonstrates broad protection against SARS-CoV-2 variants, with highly attenuated replication and minimal lung pathology across multiple in vivo passages. The vaccine induced robust mucosal and systemic neutralizing antibodies, as well as T-cell responses, in male and female hamsters, female K18-hACE2 mice, and male HFH4-hACE2 mice. In male and female cynomolgus macaques, CDO-7N-1 effectively prevented infection, reduced severe disease, and limited transmission of SARS-CoV-2 variants. This innovative approach offers potential advantages over traditional spike-protein vaccines by providing durable protection and targeting emerging variants to curb virus transmission. Supported by ORIP (K01OD026529).
Immune Perturbation Following SHIV Infection Is Greater in Newborn Macaques Than in Infants
Shapiro et al., JCI Insight. 2024.
https://pubmed.ncbi.nlm.nih.gov/39190496
This study investigates immune perturbation following simian-human immunodeficiency virus (SHIV) infection in newborn and infant male and female rhesus macaques, highlighting significant differences in pathogenesis. Although plasma viremia and lymph node viral DNA were similar, newborns exhibited higher viral DNA levels in gut and lymphoid tissues 6–10 weeks postinfection than infants. Additionally, newborns showed greater immune alterations, with skewed monocyte and CD8+ T-cell profiles and minimal type I interferon responses. These findings suggest age-dependent immunological responses to SHIV and underscore the vulnerability of newborns to HIV-related pathogenesis, providing insights into immune development and pediatric HIV management. Supported by ORIP (P51OD011092, U42OD023038, U42OD010426) and NIAID.
Effect of Metabolic Status on Response to SIV Infection and Antiretroviral Therapy in Nonhuman Primates
Webb et al., JCI Insight. 2024.
https://pubmed.ncbi.nlm.nih.gov/39115937
This study examines how metabolic health influences the efficacy of antiretroviral therapy (ART). Using lean and obese male rhesus macaques, researchers explored the progression of simian immunodeficiency virus (SIV) infection. Obese macaques with metabolic dysfunction experienced more rapid disease progression and had a diminished response to ART than lean macaques. This study suggests metabolic health plays a significant role in HIV progression and treatment outcomes, highlighting the importance of managing metabolic conditions in people with HIV. Supported by ORIP (P51OD011092, S10OD025002), NIAID, and NIDDK.
Characterization of Collaborative Cross Mouse Founder Strain CAST/EiJ as a Novel Model for Lethal COVID-19
Baker et al., Scientific Reports. 2024.
https://www.nature.com/articles/s41598-024-77087-1
Researchers characterized the Collaborative Cross (CC) mouse model founder strain CAST/EiJ as a novel model for severe COVID-19, exhibiting high viral loads and mortality. By leveraging genetically diverse CC strains, this study identified variations in susceptibility and survival against SARS-CoV-2 variants. CAST/EiJ mice developed lung pathology and mortality despite antiviral defenses, making them a valuable tool for understanding host–pathogen interactions. The findings emphasize the utility of diverse animal models in uncovering genetic and immunological factors that influence disease outcomes, facilitating the development of targeted therapies against COVID-19 to mitigate future pandemics. Supported by ORIP (P40OD011102).
Engineered Deletions of HIV Replicate Conditionally to Reduce Disease in Nonhuman Primates
Pitchai et al., Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/39116226/
Current antiretroviral therapy (ART) for HIV is limited by the necessity for continuous administration. Discontinuation of ART leads to viral rebound. A therapeutic interfering particle (TIP) was developed as a novel single-administration HIV therapy using defective interfering particles. TIP treatment in two humanized mouse models demonstrated a significant reduction in HIV viral load. TIP intervention was completed 24 hours prior to a highly pathogenic simian immunodeficiency virus (SIV) challenge in a nonhuman primate (NHP) rhesus macaque infant model. Compared to untreated SIV infection, NHPs that received TIP treatment displayed no visible signs of SIV-induced AIDS and exhibited improved seroconversion and a significant survival advantage to the 30-week clinical endpoint. Peripheral blood mononuclear cells isolated from HIV-infected patients showed that TIP treatment reduced HIV outgrowth. This study demonstrates the potential use of a single-administration TIP for HIV treatment. Supported by ORIP (P51OD011092, U42OD010426), NCI, NIAID, and NIDA.
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.