tetano
Editor, Senior Moderator
JCI Insight
. 2021 Sep 7;150888.
doi: 10.1172/jci.insight.150888. Online ahead of print.
il-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection
Daniel Kvistad[SUP] 1 [/SUP], Suresh Pallikkuth[SUP] 2 [/SUP], Tirupataiah Sirupangi[SUP] 3 [/SUP], Rajendra Pahwa[SUP] 1 [/SUP], Alexander Kizhner[SUP] 1 [/SUP], Constantinos Petrovas[SUP] 4 [/SUP], Francois Villinger[SUP] 3 [/SUP], Savita Pahwa[SUP] 1 [/SUP]
Affiliations
Abstract
Natural aging and human immunodeficiency virus (HIV) infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody (Ab) responses to vaccines such as influenza (flu). We investigated the role of Interleukin (IL)-21, a CD4 T follicular helper cells (Tfh) regulator, on flu vaccine Ab response in non-human primates (NHPs) in the context of age and controlled simian immunodeficiency virus (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 anti-retroviral therapy. IL-21 treated animals demonstrated higher day 14 post-boost Ab responses which associated with expanded CD4+ T CM cells and peripheral (p) Tfh 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 Ab responses in SIV+ aged RM acting as an adjuvant modulating LN germinal center activity. Strategies to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population.
Keywords: AIDS/HIV; Adaptive immunity; Immunotherapy; Influenza; Vaccines.
. 2021 Sep 7;150888.
doi: 10.1172/jci.insight.150888. Online ahead of print.
il-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection
Daniel Kvistad[SUP] 1 [/SUP], Suresh Pallikkuth[SUP] 2 [/SUP], Tirupataiah Sirupangi[SUP] 3 [/SUP], Rajendra Pahwa[SUP] 1 [/SUP], Alexander Kizhner[SUP] 1 [/SUP], Constantinos Petrovas[SUP] 4 [/SUP], Francois Villinger[SUP] 3 [/SUP], Savita Pahwa[SUP] 1 [/SUP]
Affiliations
- PMID: 34491910
- DOI: 10.1172/jci.insight.150888
Abstract
Natural aging and human immunodeficiency virus (HIV) infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody (Ab) responses to vaccines such as influenza (flu). We investigated the role of Interleukin (IL)-21, a CD4 T follicular helper cells (Tfh) regulator, on flu vaccine Ab response in non-human primates (NHPs) in the context of age and controlled simian immunodeficiency virus (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 anti-retroviral therapy. IL-21 treated animals demonstrated higher day 14 post-boost Ab responses which associated with expanded CD4+ T CM cells and peripheral (p) Tfh 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 Ab responses in SIV+ aged RM acting as an adjuvant modulating LN germinal center activity. Strategies to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population.
Keywords: AIDS/HIV; Adaptive immunity; Immunotherapy; Influenza; Vaccines.