Dataset Information

Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.

ABSTRACT: Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of T_H1/T_C1/T_H17/T_C17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampens T cell receptor (TCR) signaling, mitigates terminal differentiation of effectors, and enhances the development of CD4 and CD8 T_RM cells that protect against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells play a vital role in optimal programming of CD8 T_RM and viral control. Taken together, these findings provide further insights into vaccine-induced multifaceted mucosal T cell immunity with implications in the development of vaccines against respiratorypathogens, including influenza virus and SARS-CoV-2.

SUBMITTER: Marinaik CB

PROVIDER: S-EPMC7508055 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.

Marinaik Chandranaik B CB Kingstad-Bakke Brock B Lee Woojong W Hatta Masato M Sonsalla Michelle M Larsen Autumn A Neldner Brandon B Gasper David J DJ Kedl Ross M RM Kawaoka Yoshihiro Y Suresh M M

Cell reports. Medicine 20200901 6

Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal di ...[more]

PMID: 32984856

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Project description:The adoption of pulmonary vaccines to advantageously provide superior local mucosal protection against aerosolized pathogens has been faced with numerous logistical and practical challenges. One of these persistent challenges is the lack of effective vaccine adjuvants that could be well tolerated through the inhaled route of administration. Despite its widespread use as a vaccine adjuvant, aluminum salts (alum) are not well tolerated in the lung. To address this issue, we evaluated the use of porous aluminum (Al)-based metal-organic framework (MOF) nanoparticles (NPs) as inhalable adjuvants. We evaluate a suite of Al-based MOF NPs alongside alum including DUT-4, DUT-5, MIL-53 (Al), and MIL-101-NH2 (Al). As synthesized, MOF NPs ranged between ~ 200 nm and 1 µm in diameter, with the larger diameter MOFs matching those of commercial alum. In vitro examination of co-stimulatory markers revealed that the Al-based MOF NPs activated antigen presenting cells more effectively than alum. Similar results were found during in vivo immunizations utilizing ovalbumin (OVA) as a model antigen, resulting in robust mucosal humoral responses for all Al MOFs tested. In particular, DUT-5 was able to elicit mucosal OVA-specific IgA antibodies that were significantly higher than the other MOFs or alum dosed at the same NP mass. DUT-5 also was uniquely able to generate detectable IgG2a titers, indicative of a cellular immune response and also had superior performance relative to alum at equivalent Al dosed in a reduced dosage vaccination study. All MOF NPs tested were generally well-tolerated in the lung, with only acute levels of cellular infiltrates detected and no Al accumulation; Al content was largely cleared from the lung and other organs at 28 days despite the two-dose regime. Furthermore, all MOF NPs exhibited mass median aerodynamic diameters (MMADs) of ~ 1.5-2.5 µm when dispersed from a generic dry powder inhaler, ideal for efficient lung deposition. While further work is needed, these results demonstrate the great potential for use of Al-based MOFs for pulmonary vaccination as novel inhalable adjuvants.

Dataset Information

Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.

Publications

Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.

Similar Datasets

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