Advanced search
Start date
Betweenand

Contribution of different visceral adipose compartments to oral mucosal vaccine response

Grant number: 24/23654-0
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Start date: June 01, 2025
End date: May 31, 2028
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Denise Morais da Fonseca
Grantee:Guilherme William da Silva
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

The intestinal mucosa constitutes one of the largest body surfaces exposed to the external environment, subject to microbial and dietary antigens. While it facilitates nutrient absorption, it also plays a critical role in mounting responses to pathogens and ensuring immunological tolerance to harmless antigens to maintain homeostasis. However, studies using infection models or chronic inflammatory intestinal diseases suggest that additional mechanisms, such as adjacent visceral adipose compartments, may contribute to maintaining mucosal tissue homeostasis. During my master's project (FAPESP Process 2023/04035-5), we explored the role of visceral adipose tissues, particularly the mesentery and omentum, as reservoirs of memory cells derived from oral vaccines. Our findings demonstrated that both the omentum and mesentery could serve as reservoir sites for antigen-specific T lymphocytes. In the study, we evaluated different experimental oral vaccine candidates based on the model antigen ovalbumin (OVA): Modified Vaccinia Ankara virus (MVA) as a viral vector administered sublingually; the double-mutant heat-labile toxin of Escherichia coli as an adjuvant (dmLT/OVA); and a prime-boost system using sublingual MVA followed by dmLT/OVA in that order. We observed that the dmLT/OVA platform and the prime-boost system induced the highest levels of anti-OVA IgG1 and IgG2a in serum and anti-OVA IgA in intestinal lavage compared to the other tested formulations. Furthermore, both dmLT/OVA and the prime-boost system were the most effective in promoting adaptive cellular responses, inducing Th17, CD4+CD44+, CD8+CD44+, and CD8+KI67+ T cells in the intestinal mucosa following immunization. The homologous platform using only the MVA viral vector demonstrated low immunogenicity and was associated with higher frequencies of regulatory CD4+ T cells. However, when visceral adipose tissues were evaluated, only the dmLT/OVA platform induced OVA-specific cells in the omentum and mesentery of immunized mice compared to other vaccines. This suggests that these compartments act as reservoir sites for antigen-specific T lymphocytes derived from mucosal oral vaccination. For the current project, we hypothesize that maintaining resident memory in the intestine might not be advantageous for the intestinal microenvironment or the fitness of these cells. Instead, adipose tissues adjacent to the mucosa, such as the omentum and mesentery, could act as reservoirs for memory lymphocyte populations, ensuring vaccine efficacy even under conditions that disrupt intestinal immune homeostasis. Thus, we request a transition to the PhD level to continue this study. The present project aims to elucidate the protective profile of these cells residing in visceral adipose tissues adjacent to the intestine following oral immunization with the dmLT/OVA platform, as well as the mechanisms that direct, maintain, and reestablish these cells. We believe that such antigen-specific cells exhibit protective and long-term residency in adipose tissues adjacent to the intestine. However, this protection may differ between the omentum and the mesentery. Additionally, understanding the role of these visceral adipose tissues in non-homeostatic contexts is critical to enhancing the efficacy of mucosal vaccines. Comprehending the role and importance of visceral adipose tissue in oral immunization will be crucial for demystifying its unique metabolic functions and for targeting it in the prospecting and development of mucosal vaccines.

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)