Biology subjects

Nkolola, J.

Publications and source records attributed to Nkolola, J..

4 recordsLinked to original sources

bioRxiv2026

Displayed and Encoded Antigens on Adenovirus Vectors Optimize Humoral and Cellular Immune Responses in Rhesus Macaques

Adenovirus vector-based vaccines were deployed widely during the COVID-19 pandemic. In this study, we explored the potential of displaying an antigen on the surface of the adenovirus capsid as well as encoding an antigen as a transgene in the adenovirus vector to optimize both humoral and cellular immune responses. We show that displaying SARS-CoV-2 Spike receptor biding domain (RBD) on the Ad5 capsid while simultaneously encoding Spike as a transgene induced robust antibody and T cell responses in rhesus macaques. These data demonstrate that adenoviruses can be utilized simultaneously as both nanoparticle scaffolds and viral vectors.

immunology↗

bioRxiv2024

Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused a global pandemic in 2016-2017 with continued ongoing transmission at low levels in several countries. In the absence of an approved ZIKV vaccine, neutralizing monoclonal antibodies (mAbs) provide an option for the prevention and treatment of ZIKV infection. Previous studies identified a potent neutralizing human mAb ZIKV-117 that reduced fetal infection and death in mice following ZIKV challenge. In this study, we report exquisite potency of ZIKV-117 in a titration study in rhesus macaques to protect against ZIKV challenge. We show complete protection at a dose of 0.016 mg/kg ZIKV-117, which resulted in median serum concentrations of 0.13 {micro}g/mL. The high potency of this mAb supports its potential clinical development as a novel biotherapeutic intervention for ZIKV. ImportanceIn this study, we report the potency of the ZIKV-specific neutralizing antibody ZIKV-117 against ZIKV challenge in a titration study rhesus macaques. This high potency supports the further development of this mAb for ZIKV.

microbiology↗

bioRxiv2021

A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in rhesus macaques

Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention, post-exposure prophylaxis, or therapy. However, the titer of neutralizing antibodies required for protection against SARS-CoV-2 infection remains poorly characterized. We previously described two potently neutralizing mAbs COV2-2130 and COV2-2381 targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein. Here, we engineered the Fc-region of these mAbs with mutations to extend their persistence in humans and reduce interactions with Fc gamma receptors. Passive transfer of individual or combinations of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route conferred virological protection in a non-human primate (NHP) model of SARS-CoV-2 infection, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined 6,000 as a protective serum neutralizing antibody titer in NHPs against infection for passively transferred human mAbs that acted by direct viral neutralization, which corresponded to a concentration of 20 g/mL of circulating mAb.

immunology↗

bioRxiv2020

Integrated technology platform for accelerated discovery of antiviral antibody therapeutics

The emergence and reemergence of highly virulent viral pathogens with pandemic potential has created an urgent need for accelerated discovery of antiviral therapeutics. Antiviral human monoclonal (mAbs) are promising drug candidates to prevent or treat severe viral diseases, but the long timelines needed for discovery limits their rapid deployment and use. Here, we report the development of an integrated sequence of technologies incorporating advances in single-cell mRNA sequence analysis, bioinformatics, synthetic biology, and high-throughput functional analysis that allowed us to discover highly potent antiviral human mAbs and validate their activity in vivo at an unprecedented scale, speed, and efficiency. In a 78-day study, modeling deployment of a rapid response platform to an outbreak, we isolated >100 individual Zika virus (ZIKV) specific human mAbs, assessed their function, identified 29 broadly-neutralizing mAbs, and verified therapeutic potency of lead candidates with antibody-encoding mRNA formulation and/or IgG protein delivery in mice and nonhuman primates. Our work provides a roadmap for the rapid antibody discovery programs against viral pathogens of global concern.

immunology↗