Biology subjects

Rogers, K.

Publications and source records attributed to Rogers, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Plasmodium berghei is resistant to aryl amino acetamides that inhibit P. falciparum growth by targeting the phospholipid transfer protein PfSTART1.

In a previous screen for compounds that inhibit Plasmodium falciparum merozoite invasion of red blood cells, we identified the Medicines for Malaria Venture compound MMV006833. This compound inhibits PfSTART1, a protein implicated in the expansion of the nascent parasitophorous vacuole membrane following invasion, to accommodate the developing ring-stage parasite. Live-cell lattice light-sheet microscopy of invading merozoites revealed that mNeonGreen-tagged PfSTART1 is released from structures within the merozoite into the nascent parasitophorous vacuole approximately 109 seconds after invasion. Expansion microscopy of PfSTART1-HA merozoites further showed that these punctate PfSTART1-containing structures do not colocalise with known secretory organelles (rhoptries, micronemes and dense granules). Although analogues of MMV006833 are highly potent against P. falciparum, they were previously found to be ineffective against P. berghei parasites in the mouse malaria model. Here, we demonstrate that PbSTART1 is highly resistant to MMV006833 and its analogues when expressed in P. falciparum, indicating that structural differences between the orthologous proteins reduce inhibitor potency. The crystal structure of PfSTART1 in complex with WEHI-991 revealed the molecular basis for inhibition and provided a structural explanation for the reduced potency of this family of compounds against P. berghei. To sensitise P. berghei parasites to MMV006833 analogues, the parasites were engineered to express PfSTART1; however, these chimeric parasites remained insensitive to the compounds. This suggests that factors beyond target engagement, such as compound half-life or bioavailability, contribute to the lack of efficacy observed in the mouse malaria model.

microbiology↗

bioRxiv2026

Oxytocin and Vasopressin at Birth Prevent Hypoactivity and Excess Weight Gain in Vole Offspring Delivered by Cesarean Section

Birth occurs during a sensitive period in brain development wherein hormones facilitate the dramatic shift in physiology that accomplishes the transition to extrauterine homeostasis. The surge in birth signaling hormones is abridged in cases of delivery by cesarean section (CS), which accounts for 32% of all births in the U.S. Epidemiological studies have associated birth via CS with increased risk of obesity in later life. Here, we sought to investigate this association using an experimental preclinical animal model, the prairie vole. Subjects were delivered either via vaginal delivery (VD) or CS and then cross-fostered. CS delivery led to increased body weight across development, which could be prevented with hormone rescue of oxytocin (OXT) and arginine vasopressin (AVP), delivered to neonates immediately after CS. This weight gain could not be attributed to differences in birth weight, parenting, food consumption, or thermoregulation; however, CS subjects moved slower than VD subjects, which hormone rescue reversed. Hormone rescue also reduced adiposity in adulthood among CS subjects. The dopamine system was dysregulated in the caudate/putamen of CS offspring, suggesting a neural mechanism for the decreased locomotion. Hormone rescue of CS neonates restored dopamine synthesis in the caudate/putamen and increased spontaneous locomotor activity. These findings suggest CS can lead to increased weight gain in part through a reduction of locomotion driven by long-lasting changes in striatal dopamine regulation, all of which can be prevented by treating CS neonates with a single peripheral administration of two birth-signaling hormones, OXT and AVP.

neuroscience↗

bioRxiv2026

WildAlert: A Real-Time, AI-Driven Early Warning System for Wildlife Health and Ecological Threat Detection

Emerging infections and environmental disruptions increasingly threaten wildlife and ecosystem health. Free-ranging wildlife often serve as early indicators of ecological instability, making timely detection of morbidity and mortality events critical for early warning. Yet, existing systems lack the analytical capacity for real-time outbreak detection. We present WildAlert, an AI-driven early warning system that integrates fine-tuned BERT-based natural language processing models with unsupervised anomaly detection framework to identify unusual wildlife health events using real-time pre-diagnostic clinical data from wildlife rehabilitation organizations. The NLP module achieved high accuracy across clinical classifications and circumstances of admissions, enabling a pre-diagnostic syndromic surveillance framework. Retrospective validation demonstrated that WildAlert anomalies frequently coincided with or preceded confirmed morbidity events, including highly pathogenic avian influenza (HPAI), harmful algal bloom-associated toxicosis, cold-stunning in sea turtles, mass stranding events, West Nile virus, and mycoplasmosis. WildAlert establishes the worlds largest standardized, near real-time wildlife health surveillance system, transforming wildlife rehabilitation clinical records into actionable intelligence capable of detecting anomalies across taxa and regions, often before other surveillance methods. WildAlert provides a transferable analytical framework and scalable One Health model linking biodiversity monitoring, zoonotic disease preparedness, and ecosystem-linked environmental threats, with implications for conservation, public health and environmental hazard response.

ecology↗

bioRxiv2025

Differentiation of Toxoplasma into latent forms is linked to central carbon metabolism and requires a GID/CTLH-type E3 ubiquitin ligase

Toxoplasma and other Apicomplexan parasites, switch between different developmental stages to persist in and transmit between hosts. Toxoplasma can alternate between systemic tachyzoites and encysted bradyzoite forms found in the CNS and muscle tissues. How parasites sense these tissue types and trigger differentiation remains largely unknown. We show that Toxoplasma differentiation is induced under glucose-limiting conditions and using a CRISPR screen identify parasite genes required for growth under these conditions. From [~]25 identified genes important for differentiation we show that lactate and glutamine metabolism is linked to differentiation and demonstrate the importance of an E3 ubiquitin ligase complex, orthologous to glucose induced degradation deficient (GID) complex in yeast and CTLH complex in humans. We show that TgGID likely regulates translational repression of a key transcription factor required for differentiation, BFD1, through its 3 utr. Overall, this work provides important new insight into how these divergent parasites sense different host cell niches and trigger stage conversion through a ubiquitination-dependent program.

microbiology↗

bioRxiv2025

Climate-driven mangrove dieback and recovery: a case study in Albert and Leichhardt Rivers, Australia

A severe dieback event occurred in 2015/2016 in the Gulf of Carpentaria, northern Australia, which was later attributed to El Nino-Southern Oscillation (ENSO) and unusually low sea levels associated with the lunar nodal cycle. However, the long-term drivers of mangrove changes, their resilience, and species-specific responses to these environmental events remain insufficiently understood. This study applies an integration of k-means clustering and random forest classification on the Landsat archive to address knowledge gaps regarding mangrove dynamics. Despite episodic dieback in 2002/2004 (9.1 km2), 2008 (2.9 km2), and 2015/2016 (8.1 km2), mangrove zones showed a net increase in area (+260%, from 21.4 km2 to 55.7 km2) and greenness (NDVI, +18%) over the period 1987-2023. These results indicate cyclical patterns of decline in extent and condition followed by rapid recovery. Landward edges, dominated by Avicennia marina, presented the lowest NDVI values during extreme negative ENSO phases, particularly when unusually low sea levels driven by the lunar nodal cycle further reduced tidal inundation. This pattern suggests greater vulnerability to water deficits and salinity stress in these zones. The mature R. stylosa dominated areas in the central zone of the mangrove forest remained stable throughout the study period, and significant progradation was observed at the seaward margins, dominated by A. marina, likely driven by sediment accretion during increased river discharge years. This highly dynamic mangrove forest demonstrates capacity to extend both landwards and seawards. However, as climate variability intensifies, particularly with more frequent extreme events and shifting tidal regimes projected with sea-level rise, understanding the long-term resilience of mangrove forests and their capacity to recover will be crucial for informing conservation strategies focused on specific zones and maintaining blue carbon stocks of mature mangrove forests.

ecology↗

bioRxiv2025

Impact of Cesarean Delivery on Reward Behavior and Neurodevelopment in Adult Prairie Vole Offspring

Accumulating clinical evidence has shown that birth by Cesarean section (CS) is associated with a higher incidence of disorders involving the dysregulation of dopamine (DA), such as attention deficit-hyperactivity disorder, autism spectrum disorder, and obesity, compared to vaginal delivery (VD). The mesolimbic (ML) system encompasses DAergic neurons that modulate reward processes underlying learning, motivation, and food intake. Previous research has shown that there are lower levels of DA in the prefrontal cortex and higher in the nucleus accumbens (NAc) of CS offspring. Alterations in the ML-DA system as a consequence of birth via CS may impact behavioral response to rewarding stimuli, such as food. Thus, we aimed to ascertain the behavioral and neurodevelopmental outcomes relevant to food reward in CS prairie vole offspring. This study utilized conditioned place preference (CPP) testing to assess learning using context-dependent conditioning, operant conditioning to assess acquisition of a conditioned response and motivation to receive a reinforcer, and immunohistochemistry (IHC) to stain for tyrosine hydroxylase (TH) in the NAc. Behavioral results showed no difference in preference for the conditioned chamber during CPP testing between CS offspring and their VD counterparts. CS prairie vole offspring had a lower average break point during progressive-ratio testing compared to VD offspring, but no difference in response during fixed-ratio 1 or 3 testing. IHC results showed CS offspring had lower levels of TH-immunoreactivity in the NAc core and shell. These findings further support that delivery by CS has long-term neurodevelopmental effects, specifically in the brains reward system, and that CS offspring have decreased motivation toward food reward independent of deficits in learning.

neuroscience↗

bioRxiv2024

Comparative genomics of the sexually transmitted parasite Trichomonas vaginalis reveals relaxed and convergent evolution and genes involved in spillover from birds to humans

Trichomonas vaginalis is the causative agent of the venereal disease trichomoniasis which infects men and women globally and is associated with serious outcomes during pregnancy and cancers of the human reproductive tract. Trichomonads parasitize a range of hosts in addition to humans including birds, livestock, and domesticated animals. Recent genetic analysis of trichomonads recovered from columbid birds has provided evidence that these parasite species undergo frequent host-switching, and that a current epoch spillover event from columbids likely gave rise to T. vaginalis in humans. We undertook a comparative evolutionary genomics study of seven trichomonad species, generating chromosome-scale reference genomes for T. vaginalis and its avian sister species Trichomonas stableri, and assemblies of five other species that infect birds and mammals. Human-infecting trichomonad lineages have undergone recent and convergent genome size expansions compared to their avian sister species, and the major contributor to their increased genome size is increased repeat expansions, especially multicopy gene families and transposable elements, with genetic drift likely a driver due to relaxed selection. Trichomonads have independently host-switched twice from birds to humans, and genes implicated in the transition to the human host include those associated with host tissue adherence and phagocytosis, extracellular vesicles, and CAZyme virulence factors.

microbiology↗

bioRxiv2024

Direct measurement of PIP2 densities in biological membranes using a peptide-based sensor

Organization and composition of the plasma membrane are important modulators of many cellular programs. Phosphatidylinositol phosphate (PIP) lipids are low abundance membrane constituents with different arrangements of phosphate groups around an inositol head group that regulate a large number of signaling pathways. Many strategies have been developed to detect and track PIP species to monitor their clustering, mobility, and interaction with binding partners. We implement a peptide-based ratiometric sensor for the detection of PI(4,5)P2 lipids in reconstituted membrane systems that permit absolute quantification of PI(4,5)P2 densities down to physiological levels. The sensor is membrane permeable and easily applicable to measurements in living cells. Application of calibrated sensors to cells expressing common mutations in the small GTPase, Ras, showed a reshaping of surface PI(4,5)P2 levels and distributions in a mutation-specific manner. The rapid implementation of this quantitative sensing strategy to cellular studies of cellular signaling, membrane organization and dynamics should be broadly applicable.

biochemistry↗

bioRxiv2024

Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection

Developing vaccines that promote CD8+ T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+ stem cell-like memory T (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements for TSCM formation are unclear. Here, we identify the temporal window for type I interferon (IFN-I) receptor (IFNAR) blockade to drive TSCM cell generation. TSCM cells were transcriptionally distinct and emerged from a transitional precursor of exhausted (TPEX) cellular state concomitant with viral clearance. TSCM differentiation correlated with T cell retention within the lymph node paracortex, due to increased CXCR3 chemokine abundance which disrupted gradient formation. These affects were due a counterintuitive increase in IFN{psi}, which controlled cell location. Combining IFNAR inhibition with mRNA-LNP vaccination promoted specific TSCM differentiation and enhanced protection against chronic infection. These finding propose a new approach to vaccine design whereby modulation of inflammation promotes memory formation and function. HIGHLIGHTSO_LIEarly, transient inhibition of the type I interferon (IFN) receptor (IFNAR) during acute viral infection promotes stem cell-like memory T (TSCM) cell differentiation without establishing chronic infection. C_LIO_LITSCM and precursor of exhausted (TPEX) cellular states are distinguished transcriptionally and by cell surface markers. C_LIO_LIDevelopmentally, TSCM cell differentiation occurs via a transition from a TPEX state coinciding with viral clearance. C_LIO_LITransient IFNAR blockade increases IFN{psi} production to modulate the ligands of CXCR3 and couple TSCM differentiation to cell retention within the T cell paracortex of the lymph node. C_LIO_LISpecific promotion of TSCM cell differentiation with nucleoside-modified mRNA-LNP vaccination elicits enhanced protection against chronic viral challenge. C_LI

immunology↗

bioRxiv2024

Soil carbon in the world's tidal marshes

Tidal marshes are threatened coastal ecosystems known for their capacity to store large amounts of carbon in their water-logged soils. Accurate quantification and mapping of global tidal marshes soil organic carbon (SOC) stocks is of considerable value to conservation efforts. Here, we used training data from 3,710 unique locations, landscape-level environmental drivers and a newly developed global tidal marsh extent map to produce the first global, spatially-explicit map of SOC storage in tidal marshes at 30 m resolution. We estimate the total global SOC stock to 1 m to be 1.44 Pg C, with a third of this value stored in the United States of America. On average, SOC in tidal marshes 0-30 and 30-100 cm soil layers are estimated at 83.1 Mg C ha-1 (average predicted error 44.8 Mg C ha-1) and 185.3 Mg C ha-1 (average predicted error 105.7 Mg C ha-1), respectively. Our spatially-explicit model is able to capture 59% of the variability in SOC density, with elevation being the strongest driver aside from soil depth. Our study reveals regions with high prediction uncertainty and therefore highlights the need for more targeted sampling to fully capture SOC spatial variability.

ecology↗

bioRxiv2024

The subthalamic nucleus contributes causally to perceptual decision-making in monkeys

The subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an "accumulate-to-bound"-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.

neuroscience↗

bioRxiv2023

Spatial analysis of Hofbauer cell transcriptome, distribution and morphology in placentas exposed to Plasmodium falciparum

Placental infection remains a significant health burden for mothers and their babies in low-income countries, especially in sub-Saharan Africa, where malaria transmission is intense. An increase in inflammatory biomarkers and poor vascularisation are characteristics of placentas infected with malaria. Hofbauer cells (HBCs) - placental villous macrophages of fetal origin - are one of the most abundant immune cells in the placenta. HBCs are thought to have roles in angiogenic processes and have been linked with the pathophysiology of several infections and inflammatory conditions during pregnancy, including malaria (caused by Plasmodium falciparum). However, there is limited in situ data on the transcriptional, proteomic or morphologic profile of these cells either during or following clearance of P. falciparum infection. We leveraged placental samples prospectively collected at delivery from 610 Malawian women enduring a high burden of malaria and other infections and nutritional deficiencies. We profiled placentas through spatial transcriptomic and proteomic platforms to discern in situ HBC features that could distinguish placentas with or without evidence of past malaria. In this cohort, past placental infection was common and was associated with lower birth weight babies (adjusted effect [95% confidence interval], -80.9 [-165.9, -3.7] g, P= 0.040). However, at term, HBC numbers, abundance, and transcriptional profiles from placentas with evidence of past infection were similar to those of placentas without malaria. HBCs may recover post-infection back to a basal state or may be replaced in the tissue over the course of pregnancy. Placentas with evidence of past malaria did show evidence of reduced fetal vessel development (mean area difference: -22.8% [-37.6, -7.9], P=0.003). Reduced vascular development following infection early in pregnancy may reflect disturbances to the normal vasculogenic and angiogenic processes, of which HBCs are an integral part.

immunology↗

bioRxiv2023

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

immunology↗

bioRxiv2023

Aryl amino acetamides prevent the development of Plasmodium falciparum rings via inhibition of the lipid transfer protein PfSTART1

With resistance to most antimalarials increasing, it is imperative that new antimalarial drugs are developed to replace or complement front-line artemisinin therapies. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited ring development of newly invaded merozoites. Here, we selected parasites resistant to M-833 and identified independent mutations arising in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introduction of the identified PfSTART1 mutations into wildtype parasites reproduced resistance to both M-833 and highly potent analogues, confirming PfSTART1 mutations were sufficient to confer resistance. The analogues bound to recombinant PfSTART1 with nanomolar affinity. We also demonstrated selective PfSTART1 engagement by the analogues using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assay for the first time in Plasmodium. Imaging of newly invaded merozoites showed the inhibitors prevented the conversion into larger amoeboid ring-stage parasites potentially through the inhibition of phospholipid transfer from the parasite to the encasing parasitophorous vacuole membrane (PVM) and/or within the parasite. We show that these PfSTART1 inhibitors also block transmission. With multiple stages of the parasites lifecycle being targeted by PfSTART1 inhibitors, this protein therefore represents a novel drug target with a new mechanism of action.

cell biology↗

bioRxiv2023

An immunohistochemical atlas of necroptotic pathway expression

Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators - Caspase-8, RIPK1, RIPK3 and MLKL - in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo. HighlightsO_LI13 automated immunohistochemistry protocols for detecting the necroptotic pathway C_LIO_LINecroptotic pathway expression is confined to fast-cycling immune barriers C_LIO_LINecroptotic pathway expression changes at sites of immunoinflammatory challenge C_LIO_LIImmunodetection of necrosomes in IBD patients is a putative new diagnostic tool C_LI

cell biology↗

bioRxiv2023

Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth

Trabid/ZRANB1 missense mutations have been identified in children diagnosed with a range of congenital disorders including reduced brain size, but how Trabid regulates neurodevelopment is not understood. We have characterised these patient mutations in cells and mice to identify a key role for Trabid in the regulation of neurite growth. One of the patient mutations flanked the catalytic cysteine of Trabid and its deubiquitylating (DUB) activity was abrogated. The second variant retained DUB activity, but failed to bind STRIPAK, a large multiprotein assembly implicated in cytoskeleton organisation and neural development. Trabid/ZRANB1 knock-in mice harbouring either of these patient mutations exhibited reduced neuronal and glial cell densities in the brain and a motor deficit consistent with fewer dopaminergic neurons and projections. Mechanistically, both DUB-impaired and STRIPAK-binding-deficient Trabid variants impeded the trafficking of adenomatous polyposis coli (APC) to microtubule plus-ends. Consequently, the formation of neuronal growth cones and the trajectory of neurite outgrowth from mutant midbrain progenitors were severely compromised. We propose that STRIPAK recruits Trabid to deubiquitylate APC, and that in cells with mutant Trabid, APC becomes hyperubiquitylated and mislocalised causing impaired organisation of the cytoskeleton that underlie the neuronal and developmental phenotypes.

cell biology↗

bioRxiv2022

Safety and biodistribution of NanoligomersTM targeting SARS-CoV-2 genome for treatment of COVID-19

As the world braces to enter its third year in the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed after three separate administration methods, namely intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.

bioengineering↗

bioRxiv2022

Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-{beta} (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3x107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.

immunology↗