Systems Investigation of Vaccine Responses in Aging and Frailty

This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose).

Contact Information

Office/Contact: Irene Matos, RN
Phone: 203-737-4739
Email: irene.matos@yale.edu
 

Designer Flu Proteins: A New Approach to Universal Influenza Vaccines

Tiny Nanoparticles Could Be A Big Jump for Flu Vaccines

NIAID Begins Universal Flu Vaccine Study

Andre Ballesteros-Tato, Ph.D.

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Adaptive Immunity and Immunoregulation Section
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Program Description

The overall goal of the Adaptive Immunity and Immunoregulation Section is to define the cellular and molecular mechanisms that regulate the balance between protective and pathogenic adaptive immune responses to allergens. Ultimately, our research aims to develop new immunotherapies to treat and prevent food and respiratory allergies without inducing profound immunosuppression.

We focus on three main areas:

  1. Tolerance vs. Inflammation: Tolerance prevents immune overactivation and maintains tissue homeostasis, while inflammation is critical for fighting infections. However, when these processes occur simultaneously, inflammation can disrupt tolerance, amplifying immune responses to harmless antigens such as allergens. Conversely, persistent allergic reactions can induce cellular and environmental changes that impair responses to pathogens and vaccines. We study how viral infections contribute to allergic responses and how allergies affect immune responses to pathogens. This knowledge is vital for designing therapies that prevent unwanted immune responses while preserving protective immunity.
  2. T Follicular Helper (Tfh) Cells: Tfh cells are crucial for supporting B cells and maintaining germinal centers. Recent findings from our lab have revealed that Tfh cells are more diverse than previously expected, secreting effector cytokines and playing broader regulatory roles. There is also growing evidence of an ontogenetic link between Tfh cells and other effector and regulatory T cell subsets. We study Tfh cell plasticity and heterogeneity, exploring their impact on tolerance induction and allergy development.
  3. Lung-Resident Memory T and B Cells: Lung-resident memory T and B cells are non-circulating memory cells that develop in response to respiratory challenges and permanently reside in the lungs. While the role of tissue-resident memory cells in response to respiratory pathogens has been established, their involvement in respiratory allergies remains elusive. We investigate how allergen-specific lung-resident memory T and B cells are generated and maintained, defining the factors controlling tissue memory generation and assessing their role in allergic responses. We also evaluate the potential of targeting these cells to prevent allergic reactions.

By integrating these projects, we aim to elucidate the complex mechanisms that balance protective and pathogenic immune responses and generate the necessary knowledge to develop novel treatments for food and respiratory allergies.

Selected Publications

Arroyo-Díaz NM, Bachus H, Papillion A, Randall TD, Akther J, Rosenberg AF, León B, Ballesteros-Tato A. Interferon-γ production by Tfh cells is required for CXCR3+ pre-memory B cell differentiation and subsequent lung-resident memory B cell responses. Immunity. 2023 Oct 10;56(10):2358-2372.e5.

Jenkins MM, Bachus H, Botta D, Schultz MD, Rosenberg AF, León B, Ballesteros-Tato A. Lung dendritic cells migrate to the spleen to prime long-lived TCF1hi memory CD8+ T cell precursors after influenza infection. Sci Immunol. 2021 Sep 10;6(63):eabg6895.

León B, Ballesteros-Tato A. Modulating Th2 Cell Immunity for the Treatment of Asthma. Front Immunol. 2021 Feb 10;12:637948.

Papillion A, Powell MD, Chisolm DA, Bachus H, Fuller MJ, Weinmann AS, Villarino A, O'Shea JJ, León B, Oestreich KJ, Ballesteros-Tato A. Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-TFH cells. Sci Immunol. 2019 Sep 13;4(39):eaaw7636.

Botta D, Fuller MJ, Marquez-Lago TT, Bachus H, Bradley JE, Weinmann AS, Zajac AJ, Randall TD, Lund FE, León B, Ballesteros-Tato A. Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection. Nat Immunol. 2017 Nov;18(11):1249-1260.

León B, Bradley JE, Lund FE, Randall TD, Ballesteros-Tato A. FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability. Nat Commun. 2014 Mar 17;5:3495.

Visit PubMed for a complete publications listing.

Major Areas of Research
  • Characterize the mechanisms controlling adaptive immune responses, particularly memory T and B cells and T follicular helper cells, in the context of food and respiratory allergies
  • Investigate how infections contribute to the development of allergies and how allergies, in turn, affect immune responses to pathogens and vaccines
  • Develop novel immunotherapies that balance protection and immunosuppression for food and respiratory allergens

DHVI Receives Contract to Manufacture Investigational Avian Flu Vaccines

TFF Pharmaceuticals Announces Positive Preclinical Data from Bivalent Universal Influenza Vaccine Candidates Manufactured by TFF Following Intranasal Immunization

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TFF Pharmaceuticals
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TFF Pharmaceuticals Announces Positive Preclinical Data
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T Helper Cells May Be the Key to Improving Annual Influenza Vaccines

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St. Jude Children’s Research Hospital
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T Helper Cells May Be the Key to Improving Annual Influenza Vaccines
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Bird Flu Stays Stable on Milking Equipment for at Least One Hour, Pitt Research Finds

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University of Pittsburgh School of Medicine
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Bird Flu Stays Stable on Milking Equipment for at Least One Hour, Pitt Research Finds
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Features of H5N1 Influenza Viruses in Dairy Cows May Facilitate Infection, Transmission in Mammals

A series of experiments with highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses circulating in infected U.S. dairy cattle found that viruses derived from lactating dairy cattle induced severe disease in mice and ferrets when administered via intranasal inoculation. The virus from the H5N1-infected cows bound to both avian (bird) and human-type cellular receptors, but, importantly, did not transmit efficiently among ferrets exposed via respiratory droplets.

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