Biology subjects

Rogers, K. A.

Publications and source records attributed to Rogers, K. A..

6 recordsLinked to original sources

bioRxiv2026

Sustained Delivery of a SARS-CoV-2 Subunit Vaccine in An Adjuvanted Hydrogel Depot Enhances Vaccine Responses in Nonhuman Primates

While natural infections expose the immune system for days to weeks of inflammation and antigen presentation, immunizations with conventional bolus vaccines often lead to rapid clearance of antigens and adjuvants. Prolonged exposure to vaccines using controlled delivery devices or repeated dosing regimens has been shown to enhance germinal center reactions, leading to improved humoral responses, including increased magnitude of antibody titers and enhanced neutralizing activity. Herein, we report the use of injectable polymer-nanoparticle (PNP) hydrogels as a vaccine depot technology for sustained delivery of the clinically relevant SARS-CoV-2 Hexapro subunit antigen and a toll-like receptor agonist adjuvant. In mice, we demonstrated that PNP hydrogel vaccines enhanced germinal center responses and antibody responses relative to bolus vaccination. In nonhuman primates, hydrogel vaccines induced enhanced and durable antibody responses against wildtype and variants of concern such as Omicron BA.5 compared to bolus vaccination. We report the first use of a biomaterials-based approach for sustained delivery of vaccines in nonhuman primates, further advancing toward clinical translation.

bioengineering↗

bioRxiv2025

Diabetes mellitus affects urinary tissue tropism of group B streptococci in a sex-dependent manner

Diabetes mellitus (DM) increases susceptibility to Streptococcus agalactiae (group B Streptococcus or GBS) urinary tract infections (UTI) and their exacerbations such as ascending pyelonephritis and sepsis, although underlying molecular mechanisms have not been fully deciphered. To address our hypothesis that DM mediated alterations in the host urinary immune defenses increase susceptibility to GBS-UTI, we inoculated, via transurethral route, GBS strain 10/84 into the urinary bladders of 8 weeks old, male and female, diabetic (obese, hyperglycemic mice denoted as D) and non-diabetic (ND) mouse littermates. At 24 h post-infection (hpi), compared to their ND littermates, the D-mice showed significantly higher GBS CFUs in the bladder, the kidneys, and the spleen. This was accompanied by a significantly reduced recruitment of CD45+ leukocytes to and suppression of pro-inflammatory cytokine production in GBS-infected D-bladder and D-kidneys compared to their ND counterparts. We also noted sex-dependent differences in GBS urinary tissue tropism. For example, D-females exhibited significantly higher bladder burden compared to ND-females, D-males, and to ND-males, while the bladder burden in ND-females was not significantly different from that in ND-males. In contrast, ND-males showed significantly higher kidney CFUs than ND-females and DM further increased kidney CFU burden in males. GBS-induced recruitment of CD45+ leukocytes was not different between male and female mice within either D or ND cohorts. GBS-UTI induced significantly higher CXCL1 production in male bladders in both D and ND cohorts compared to their female counterparts. These results indicate that DM increases susceptibility to GBS-UTI and the dissemination to spleen by affecting leukocyte recruitment and pro-inflammatory cytokine production in a sex-dependent manner. ImportanceIn this study we sought to understand why diabetic individuals are more susceptible to urinary tract infections (UTI) by Gram positive Streptococcus agalactiae (group B Streptococcus or GBS). We induced UTI by inoculating GBS into the bladders of diabetic (obese, hyperglycemic) and non-diabetic, male and female mice. At 24 hours after infection, compared to the non-diabetic mice, the diabetic mouse urinary tracts showed higher GBS counts and reduced immune defenses. Diabetes also promoted dissemination of GBS to the spleen. Furthermore, female diabetic mice were more susceptible to bladder infection while diabetes worsened the increased overall susceptibility of males to kidney infection, a difficult-to-treat, potentially life threatening exacerbation of GBS-UTI. Overall, our results suggest that both diabetes and sex are important determinants of susceptibility to GBS-UTI and resulting severe outcomes.

microbiology↗

bioRxiv2022

NLRP3 inflammasome is dispensable in methicillin resistant Staphylococcus aureus urinary tract infection

NLRP3 inflammasome is a cytoplasmic complex that senses molecular patterns from pathogens or damaged cells to trigger an innate immune defense response marked by the production of proinflammatory cytokines IL-1{beta} and IL-18 and an inflammatory death called pyroptosis. The NLRP3 inflammasome is activated in the urinary tract by a variety of infectious and non-infectious insults. In this study, we investigated the role of NLRP3 inflammasome by inducing methicillin resistant Staphylococcus aureus (MRSA) ascending UTI in WT and Nlrp3-/- mice. At 24 and 72 hpi, compared to the WT, the MRSA-infected Nlrp3-/- showed [~]100-fold lower median CFUs, although this reduction was not statistically significant. The ablation of NLRP3 did not affect MRSA-induced urinary immune defenses as indicated by the similar levels of pro-inflammatory cytokines and chemokines and the similar numbers of granulocytes in the bladder and the kidneys of WT and Nlrp3-/- mice at 24 h after MRSA infection. However, MRSA-infected Nlrp3-/- bladders, but not kidneys, showed significantly higher monocyte infiltration. The histopathological analysis of bladder and kidney sections showed similar inflammation in MRSA-infected Nlrp3-/- and WT mice. Overall, these results suggest that MRSA-induced urinary NLRP3 activity is dispensable to the host. ImportanceIndwelling urinary catheter usage increased susceptibility to methicillin-resistant Staphylococcus aureus (MRSA) urinary tract infections (UTI) which can be difficult to treat and can result in potentially fatal complications such as bacteremia, urosepsis, and shock. In this work, we examined the role of NLRP3 inflammasome in MRSA uropathogenesis. In comparison to the WT, mice deficient in NLRP3 activity showed similar MRSA burden and similar inflammation in the bladder and kidney tissues at 24 h after the experimental induction of ascending UTI. These results suggest that NLRP3 inflammasome is not involved in shaping urinary immune defenses during acute MRSA-UTI.

immunology↗

bioRxiv2022

Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOC) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOC. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses against VOC, as compared to non-human primates or humans, suggesting caution should be exercised when interpreting data for this animal model.

immunology↗

bioRxiv2021

Localization of infection in neonatal rhesus macaques after oral viral challenge

While vertical transmission of human immunodeficiency virus (HIV) can occur in utero and during delivery and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection. Author SummaryApproximately 1.8 million children are currently living with human immunodeficiency virus (HIV). While mother-to-child HIV transmission can occur in utero and during delivery, it most commonly occurs through breastfeeding, creating the need to understand how the virus moves throughout the body and infects the infant once breast milk is consumed. Here, we used multiple imaging techniques and PCR to determine how HIV distributes throughout the gastrointestinal tract after oral viral exposure and in which tissues and cell types become acutely infected. We found that HIV rapidly spreads throughout and penetrates the entire gastrointestinal tract as early as four hours after exposure. We also found that the intestine contained the largest number of infected cells at 96 hours and that most cells infected were T cells. Our study shows that these imaging technologies allow for the examination of viral distribution and infection in a rhesus macaque model.

cell biology↗

bioRxiv2020

PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure

HIV vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.

cell biology↗