Biology subjects

Smith, S. G.

Publications and source records attributed to Smith, S. G..

4 recordsLinked to original sources

bioRxiv2023

Rectal and vaginal challenge with mpox virus increases virus dissemination and contact transmission compared to skin challenge in the multimammate rat (Mastomys natalensis)

The 2022 mpox virus outbreak was sustained by efficient human-to-human transmission and spread predominantly through sexual networks of men who have sex with men (MSM). It is currently unclear what combination of factors resulted in the enhanced transmission. To investigate this, we established the peridomestic African rodent Mastomys natalensis as a new rodent model susceptible to infection after intraperitoneal, rectal, vaginal, and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Route-dependent shedding and tissue replication occurred in the presence of self-resolving localized skin, reproductive tract, or rectal lesions. Mucosal inoculation via both the rectal and vaginal route led to increased shedding compared to skin inoculation, and increased replication and a proinflammatory T-cell profile. Contact transmission was higher in rectally inoculated animals. This suggests that the spread in MSM communities may have been enhanced by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.

microbiology↗

bioRxiv2023

A new label-free optical imaging method for the lymphatic system enhanced by deep learning

Our understanding of the lymphatic vascular system lags far behind that of the blood vascular system, limited by available imaging technologies. We present a label-free optical imaging method that visualizes the lymphatic system with high contrast. We developed an orthogonal polarization imaging (OPI) in the shortwave infrared range (SWIR) and imaged both lymph nodes and lymphatic vessels of mice and rats in vivo through intact skin, as well as human mesenteric lymph nodes in colectomy specimens. By integrating SWIR-OPI with U-Net, a deep learning image segmentation algorithm, we automated the lymph node size measurement process. Changes in lymph nodes in response to cancer progression were monitored in two separate mouse cancer models, through which we obtained insights into pre-metastatic niches and correlation between lymph node masses and many important biomarkers. In a human pilot study, we demonstrated the effectiveness of SWIR-OPI to detect human lymph nodes in real time with clinical colectomy specimens. One Sentence SummaryWe develop a real-time high contrast optical technique for imaging the lymphatic system, and apply it to anatomical pathology gross examination in a clinical setting, as well as real-time monitoring of tumor microenvironment in animal studies.

bioengineering↗

bioRxiv2021

Induction of specific antibodies, IgG-secreting plasmablasts and memory B cells following BCG vaccination

Many tuberculosis (TB) vaccine candidates are designed as a boost to BCG; an understanding of the BCG-induced immune response is therefore critical, and the opportunity to relate this to circumstances where BCG does protect may direct the design of more efficacious vaccines. While the T cell response to BCG vaccination has been well-characterised, little is known about the B cell and antibody response. We demonstrate BCG vaccine-mediated induction of specific antibodies in different human populations and macaque species which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titres in serum versus plasma with modestly higher titres in serum. We also report for the first time the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a potential contribution of the antibody response to BCG vaccine-mediated control of mycobacterial growth in vitro. Taken together, our findings indicate that the humoral immune response in the context of BCG vaccination merits further attention to determine whether TB vaccine candidates could benefit from the induction of humoral as well as cellular immunity.

immunology↗

bioRxiv2019

Mycobacterium tuberculosis infection boosts B cell responses to unrelated pathogens

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with the related species, Mycobacterium bovis BCG, has a similar effect. This study investigated the effects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantified by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOT assays were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to tetanus toxoid (TT), diphtheria toxoid, respiratory syncytial virus, measles virus and Kaposis sarcoma herpesvirus, compared to uninfected controls. Vaccination with BCG did not alter levels of antibodies against heterologous pathogens. TT-specific antibody avidity was increased in APTB and the ratio of TT-specific plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection boosts serological memory to heterologous pathogens in human subjects and this process may be driven by polyclonal activation of memory B cells.\n\nSignificanceMycobacterium tuberculosis (M.tb) has potent immunostimulatory properties and has been used in adjuvant preparations to improve vaccine responses in animals. This study shows that natural M.tb infection in humans is associated with increased antibody and B cell recall responses to heterologous pathogens. This data suggests a potential role for M.tb antigens in immunotherapies designed to maintain antibody immunity to diverse infections.

immunology↗