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IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection
Daniel Kvistad, … , Francois Villinger, Savita Pahwa
Daniel Kvistad, … , Francois Villinger, Savita Pahwa
Published September 7, 2021
Citation Information: JCI Insight. 2021;6(20):e150888. https://doi.org/10.1172/jci.insight.150888.
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Research Article AIDS/HIV Vaccines

IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection

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Abstract

Natural aging and HIV infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody responses to vaccines such as the influenza (flu) vaccine. We investigated the role of IL-21, a CD4+ T follicular helper cell (Tfh) regulator, on flu vaccine antibody response in nonhuman primates (NHPs) in the context of age and controlled SIV mac239 infection. Three doses of the flu vaccine with or without IL-21–IgFc were administered at 3-month intervals in aged SIV+ NHPs following virus suppression with antiretroviral therapy. IL-21–treated animals demonstrated higher day 14–postboost antibody responses, which associated with expanded CD4+ T central memory cells and peripheral Tfh–expressing (pTfh–expressing) T cell immunoreceptor with Ig and ITIM domains (TIGIT), expanded activated memory B cells, and contracted CD11b+ monocytes. Draining lymph node (LN) tissue from IL-21–treated animals revealed direct association between LN follicle Tfh density and frequency of circulating TIGIT+ pTfh cells. We conclude that IL-21 enhances flu vaccine–induced antibody responses in SIV+ aged rhesus macaques (RMs), acting as an adjuvant modulating LN germinal center activity. A strategy to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population.

Authors

Daniel Kvistad, Suresh Pallikkuth, Tirupataiah Sirupangi, Rajendra Pahwa, Alexander Kizhner, Constantinos Petrovas, Francois Villinger, Savita Pahwa

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Figure 1

Influenza HAI titers.

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Influenza HAI titers.
(A) Longitudinal serum titers for the whole influe...
(A) Longitudinal serum titers for the whole influenza 2015–2016 vaccine as determined by HAI assay for healthy young (n = 4) and old (n = 4) control animals. (B) Whole vaccine HAI titer area under the curve (AUC) measured from day 98 (day 14 after B1) to day 252 (day 84 after B2) in old SIV–IL-21– (n = 4) compared with young SIV–IL-21– (n = 4) animals. (C) Longitudinal whole vaccine HAI titers of old SIV–IL-21– (n = 4) compared with old SIV+IL-21– (n = 4) animals. (D) Longitudinal whole vaccine HAI titers of old SIV+ IL-21– (n = 4) compared with old SIV+IL-21+ (n = 8) animals. (E) HAI titer AUC measured from day 182 (day 14 after B2) to day 252 (day 42 after B2) in old SIV+IL-21– (n = 4) compared with old SIV+IL-21+ (n = 8) animals. (F) Longitudinal whole vaccine HAI titers of young healthy (n = 4) compared with old SIV+IL-21+. (G) Longitudinal whole vaccine HAI titers of young SIV+IL-21– (n = 4) compared with young SIV+IL-21+ (n = 4). (H) Longitudinal whole vaccine HAI titers of young healthy (n = 4) compared with young SIV+IL21+ (n = 4). Data are displayed as mean ± SEM. HAI titer data were analyzed by mixed-effects models, with Fisher’s LSD post hoc multiple-comparison correction and 2-tailed Mann Whitney U tests performed for HAI titer AUC comparisons.

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