Biology subjects

Vijay, R.

Publications and source records attributed to Vijay, R..

3 recordsLinked to original sources

bioRxiv2025

Acute malaria dysregulates specialized lymph node macrophages to suppress vaccine-elicited protection against Ebola virus

The filovirus, Ebola virus (EBOV), causes outbreaks of Ebola virus disease (EVD) throughout equatorial Africa. ERVEBO(R) (rVSV/EBOV) is a replication-competent, recombinant vesicular stomatitis virus (rVSV)-vectored vaccine licensed to control EVD outbreaks. EVD outbreaks occur in regions endemic for Plasmodium-caused malaria. Plasmodium infections persist due in part to the parasites ability to evade sterilizing immunity which also dampens immune responses to heterologous vaccines. Acute murine Plasmodium infection at the time of rVSV/EBOV vaccination reduced vaccine-mediated protection against mouse-adapted EBOV (ma-EBOV) challenge. Decreased protection was associated with a Plasmodium-induced interferon gamma (IFN-{gamma})-mediated decrease of rVSV/EBOV replication in lymph node (LN) macrophages, resulting in reduced primary anti-EBOV glycoprotein antibody responses. Higher doses of rVSV/EBOV partially overcame the antibody deficits and elicited protective responses. Evidence of the negative impact of Plasmodium on the efficacy of low dose rVSV/EBOV vaccine protocols supports the use of high antigen loads in effective management of EVD outbreaks. IMPORTANCEWe show that blood-stage murine Plasmodium infections negatively impacts the primary antibody response elicited by low dose rVSV/EBOV vaccination and results in reduced protection against a lethal dose of ma-EBOV. This defect occurs within the draining lymph node due to the elevation of IFN-{gamma} elicted in Py-infected mice. The Py-imposed decrease in vaccine-mediated protection can be overcome with higher doses of rVSV/EBOV. While the strong protection conferred by rVSV/EBOV and significant side effects known to be associated with this vaccine have led to the suggestion that the vaccine dosage be reduced19, our studies provide a rationale for maintaining a higher dose.

microbiology↗

bioRxiv2023

Exogenous 4-1BB co-stimulation enhances memory B cell response during malaria.

T-dependent germinal center (GC) output, comprising plasma cells (PC) and memory B cells (MBC), is crucial for the clearance of Plasmodium infection and protection against reinfection. In this study, we examined the effect of an agonistic antibody targeting 4-1BB (CD137), a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), during experimental malaria. Here we show that exogenous 4-1BB stimulation, despite delaying the effector GC response, surprisingly enhanced humoral memory recall and protection from reinfection. Single cell RNA and ATAC sequencing of MBCs from mice that received 4-1BB stimulation revealed distinct populations with transcriptional and epigenetic signatures indicative of superior recall and proliferative potential. Importantly, our results indicate that the effects of 4-1BB stimulation are dependent on IL-9R signaling in B cells but independent of parasite load during primary infection. Our study proposes an immunomodulatory approach to enhance the quality of the MBC pool, providing superior protection during infection and vaccination, particularly in the context of malaria.

immunology↗

bioRxiv2022

Direct type I Interferon signaling in hepatocytes control malaria

Malaria is a devastating disease impacting over half of the worlds population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, preventing the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a novel transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary and sufficient to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire new anti-malarial drugs and vaccine strategies.

immunology↗