Strategic priming with multiple antigens can yield memory cell phenotypes optimized for infection with Mycobacterium tuberculosis: A computational study

Ziraldo, Cordelia; Gong, Chang; Kirschner, Denise E.; Linderman, Jennifer J.

doi:10.3389/fmicb.2015.01477

Title: Strategic priming with multiple antigens can yield memory cell phenotypes optimized for infection with Mycobacterium tuberculosis: A computational study

Journal Article · Wed Jan 06 00:00:00 EST 2016 · Frontiers in Microbiology

DOI:https://doi.org/10.3389/fmicb.2015.01477· OSTI ID:1239245

Ziraldo, Cordelia ^[1]; Gong, Chang ^[1]; Kirschner, Denise E. ^[1]; Linderman, Jennifer J. ^[1]

Univ. of Michigan, Ann Arbor, MI (United States)

Lack of an effective vaccine results in 9 million new cases of tuberculosis (TB) every year and 1.8 million deaths worldwide. While many infants are vaccinated at birth with BCG (an attenuated M. bovis), this does not prevent infection or development of TB after childhood. Immune responses necessary for prevention of infection or disease are still unknown, making development of effective vaccines against TB challenging. Several new vaccines are ready for human clinical trials, but these trials are difficult and expensive; especially challenging is determining the appropriate cellular response necessary for protection. The magnitude of an immune response is likely key to generating a successful vaccine. Characteristics such as numbers of central memory (CM) and effector memory (EM) T cells responsive to a diverse set of epitopes are also correlated with protection. Promising vaccines against TB contain mycobacterial subunit antigens (Ag) present during both active and latent infection. We hypothesize that protection against different key immunodominant antigens could require a vaccine that produces different levels of EM and CM for each Ag-specific memory population. We created a computational model to explore EM and CM values, and their ratio, within what we term Memory Design Space. Our model captures events involved in T cell priming within lymph nodes and tracks their circulation through blood to peripheral tissues. We used the model to test whether multiple Ag-specific memory cell populations could be generated with distinct locations within Memory Design Space at a specific time point post vaccination. Boosting can further shift memory populations to memory cell ratios unreachable by initial priming events. By strategically varying antigen load, properties of cellular interactions within the LN, and delivery parameters (e.g., number of boosts) of multi-subunit vaccines, we can generate multiple Ag-specific memory populations that cover a wide range of Memory Design Space. As a result, given a set of desired characteristics for Ag-specific memory populations, we can use our model as a tool to predict vaccine formulations that will generate those populations.

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Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1239245

Journal Information:: Frontiers in Microbiology, Vol. 6; ISSN 1664-302X

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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Increased TNF-α/IFN-γ/IL-2 and Decreased TNF-α/IFN-γ Production by Central Memory T Cells Are Associated with Protective Responses against Bovine Tuberculosis Following BCG Vaccination Maggioli, Mayara F.; Palmer, Mitchell V.; Thacker, Tyler C. Frontiers in Immunology, Vol. 7 https://doi.org/10.3389/fimmu.2016.00421	journal	October 2016

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Mekonnen, Zelalem A.; Grubor-Bauk, Branka; English, Kieran; +9 more

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

Journal Article · Thu Dec 01 00:00:00 EST 1988 · J. Virol.; (United States) · OSTI ID:1239245

Zarling, J M; Moran, P A; Brewer, L; +2 more

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59 BASIC BIOLOGICAL SCIENCES
subunit vaccine
T cell priming
cell-mediated immunity
agent-based model

Title: Strategic priming with multiple antigens can yield memory cell phenotypes optimized for infection with Mycobacterium tuberculosis: A computational study

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