Biology subjects

Mellors, J.

Publications and source records attributed to Mellors, J..

3 recordsLinked to original sources

bioRxiv2026

Spike Antibody Fc Drives Protection from SARS-CoV-2 Challenge in Macaques

A definitive correlate of protection (CoP) for SARS-CoV-2 has yet to be formally established. Previously, using data from a series of non-human primate vaccine challenge studies, we reported that neutralising antibodies (NAbs) are the strongest candidate for clinical protection against COVID-19 and that spike binding antibody is the strongest candidate CoP for viral burden post-challenge. In this study, we further characterised the protective binding antibody profile by analysing spike antibody-dependent complement deposition, Fc{gamma}R binding, isotype and antibody glycosylation. Using the machine learning platform SIMON, we demonstrate that antibody-dependent complement deposition (ADCD) and Fc{gamma}R binding are strong candidate co-correlates for each of the post-challenge outcomes; viral load and lung pathology. We found that spike antibody sialylation closely followed by Fc{gamma}R2A, was the spike antibody feature with the strongest negative correlation with histopathology score. Spike antibody ADCD, Fc{gamma}R binding, isotype and glycosylation significantly differed by immunisation regimen and sex, which demonstrates the heterogeneity of immune mechanisms induced by different immunisation platforms. We conclude that spike binding antibody, with the protective functional characteristics described herein, is a candidate CoP that captures both protection from severe clinical disease and protection against a high viral burden. These findings should be taken into consideration for future SARS-CoV-2 vaccine development.

immunology↗

bioRxiv2020

HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy

Antiretroviral therapies (ART) durably suppress HIV replication to undetectable levels - however, infection persists in the form of long-lived reservoirs of infected cells with integrated proviruses, that re-seed systemic replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in driving reductions in viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle, by querying the dynamics of HIV-specific T-cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. We show that T-cell responses to autologous reservoir viruses persist over years, and that the maintenance of HIV-Nef-specific responses was uniquely associated with residual frequencies of infected cells. These responses disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV-infected cells. These results indicate substantial visibility of the HIV reservoir to T-cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing HIV infection.

immunology↗

bioRxiv2019

Oropouche virus cases identified in Ecuador using an optimised rRT-PCR informed by metagenomic sequencing

Oropouche virus (OROV) is responsible for outbreaks of Oropouche fever in parts of South America. We recently identified and isolated OROV from a febrile Ecuadorian patient, however, a previously published rRT-PCR assay did not detect OROV in the patient sample. A primer mismatch to the Ecuadorian OROV lineage was identified from metagenomic sequencing data. We report the optimisation of an rRT-PCR assay for the Ecuadorian OROV lineage, which subsequently identified a further five cases in a cohort of 196 febrile patients. We isolated OROV via cell culture and developed an algorithmically-designed primer set for whole-genome amplification of the virus. Metagenomic sequencing of the patient samples provided OROV genome coverage ranging from 68 - 99%. The additional cases formed a single phylogenetic cluster together with the initial case. OROV should be considered as a differential diagnosis for Ecuadorian patients with febrile illness to avoid mis-diagnosis with other circulating pathogens.

genomics↗