Biology subjects

Goodwin, B.

Publications and source records attributed to Goodwin, B..

7 recordsLinked to original sources

bioRxiv2025

Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters

The long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics in Spike-specific humoral and cellular immune responses across multiple vaccine doses. While antibody titers incrementally increased and stabilized with each booster, T cell responses rapidly plateaued, maintaining remarkable stability across CD4+ and CD8+ subsets. Notably, approximately 30% of participants showed CD4+ T cell reactivity to non-Spike antigens, consistent with asymptomatic infections. Single-cell RNA sequencing revealed a diverse landscape of Spike-specific T cell phenotypes, with no evidence of increased exhaustion or significant functional impairment. However, qualitative changes were observed in individuals with evidence of asymptomatic infection, exhibiting unique immunological characteristics, including increased frequencies of Th17-like CD4+ T cells and GZMKhi/IFNR CD8+ T cell subsets. Remarkably, repeated vaccinations in this group were associated with a progressive increase in regulatory T cells, potentially indicating a balanced immune response that may mitigate immunopathology. By regularly stimulating T cell memory, boosters contribute to a stable and enhanced immune response, which may provide better protection against symptomatic infections.

immunology↗

bioRxiv2024

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies

Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. We found that the arginine-glycine-aspartate (RGD)-binding integrin 5{beta}1 is upregulated in PA endothelial cells (PAEC) and PA smooth muscle cells (PASMC) from PAH patients and remodeled PAs from animal models. Blockade of the integrin 5{beta}1 or depletion of the 5 subunit resulted in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. Using a novel small molecule integrin inhibitor and neutralizing antibodies, we demonstrated that 5{beta}1 integrin blockade attenuates pulmonary vascular remodeling and improves hemodynamics and RV function in multiple preclinical models. Our results provide converging evidence to consider 5{beta}1 integrin inhibition as a promising therapy for pulmonary hypertension. One sentence summaryThe 5{beta}1 integrin plays a crucial role in pulmonary vascular remodeling.

pathology↗

bioRxiv2023

Botanicals impact the bifidogenic effect and metabolic outputs of in vitro fiber fermentation by gut-derived microbiota in individual-specific ways

Fortification of products frequently consumed by a large proportion of society provides an attractive strategy to close the "fiber gap" and may have the potential to concomitantly reverse the detrimental health effects exacerbated by our modern diets. Besides prebiotic fibers, products can contain other functional components, e.g. botanicals. However, most studies have investigated functional components in isolation. The impact of other components present in functional product blends on the bifidogenic effect typically exerted by prebiotic fibers are largely unexplored. Here, we investigated the fiber and botanical blends included in OLIPOP, a functional soda, in an in vitro gut fermentation model. Our data revealed that the blend of inulins and resistant dextrins promoted growth of bifidobacteria across gut microbiota from four donors, even those with small initial populations. In addition, botanicals interacted with fiber fermentation in donor-specific ways, in some cases strongly enhancing fermentation rate and production of short-chain fatty acids. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/537114v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@129f0f2org.highwire.dtl.DTLVardef@89bc29org.highwire.dtl.DTLVardef@a03976org.highwire.dtl.DTLVardef@11c724c_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

Humoral and cellular immune memory to four COVID-19 vaccines

Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike--specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.

immunology↗

bioRxiv2021

SARS-CoV-2 vaccination induces immunological memory able to cross-recognize variants from Alpha to Omicron

We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.

immunology↗

bioRxiv2021

Distinguishing COVID-19 infection and vaccination history by T cell reactivity

SARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of Experimentally-defined T cell epitopes derived from the non-spike Remainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I-V-); infected and non-vaccinated (I+V-); infected and then vaccinated (I+V+); and non-infected and vaccinated (I-V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV-2 correlates of protection.

immunology↗

bioRxiv2021

Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

immunology↗