Obeid, S. | Search bioRxiv

bioRxiv2026

Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes

The yellow fever virus-17D (YFV-17D) vaccine is widely regarded as one of the most effective vaccines in existence, with protection linked to robust elicitation of neutralising antibodies1. The features of the germinal centre (GC) reaction driving this durable and potent antibody responses remain unclear. Here we examined immune dynamics in blood and lymph nodes (LNs) after primary YFV-17D immunisation in humans. Using fine needle biopsy (FNB), we identified robust T and B lymphocyte responses within draining LNs, underpinning maturation of antibodies targeting the viral envelope (E). Early antibody responses were largely IgM, with gradual accumulation of E-specific memory B cells and anti-viral IgG in the subsequent months. Monoclonal antibodies derived from GC B cells had specificity for E, with diversification in the LN capable of driving increases in binding and neutralising potency. While circulating vaccine-specific CD4+ T cells peaked two weeks post-vaccination, clonally related GC and IL-10+ T follicular helper populations progressively accumulated in the LN. Comparison of FNB transcriptional datasets following YFV-17D, SARS-CoV-2 mRNA/LNP, and seasonal influenza vaccination identified a conserved GC program involving similar B and T lymphocyte subpopulations. Collectively, we find that while YFV-17D induces robust GC activity, this trait is shared with other vaccine platforms and the notably durable protection against infection may reflect an incapacity of the virus to escape host immunity.

immunology↗

bioRxiv2021

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer.

Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion. We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. Here, we tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors. In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (ie, BNDF, TNF, FGF2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1, and reduced phosphorylated FGFR in tumors. Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multifactorial, and that weight maintenance during the peri-/post-menopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.

cancer biology↗