tetano
Editor, Senior Moderator
J Immunol
. 2022 Nov 15;209(10):1832-1836.
doi: 10.4049/jimmunol.2200577.
Cutting Edge: High-Dose Live Attenuated Influenza Vaccines Elicit Pulmonary Tissue-Resident Memory CD8+ T Cells in the Face of Pre-Existing Humoral Immunity
Ming Z M Zheng[SUP] 1 [/SUP], Svenja Fritzlar[SUP] 1 [/SUP], Zhongfang Wang[SUP] 1 2 [/SUP], Tiong Kit Tan[SUP] 3 [/SUP], Katherine Kedzierska[SUP] 1 [/SUP], Alain Townsend[SUP] 3 4 [/SUP], Patrick C Reading[SUP] 1 5 [/SUP], Linda M Wakim[SUP] 1 [/SUP]
Affiliations
Abstract
In this study, we investigated how pre-existing Ab immunity to influenza virus established from prior immunizations affects the development of CD8+ T cell responses evoked after vaccination with a live attenuated vaccine. Using a mouse model and a panel of live attenuated influenza virus vaccine candidates (cold adapted and single cycle), we show that pre-existing influenza-specific Abs directed against the vaccine backbone attenuate the size and quality of the vaccine-induced CD8+ T cell response. Importantly, we show that increasing the vaccine dose can overcome this impediment, resulting in improved vaccine-induced circulating and tissue-resident memory CD8+ T cell responses, which were protective against heterologous influenza challenge. Thus, the reduced size and quality of the T cell response elicited by a live attenuated influenza virus vaccine imparted by the influenza-specific Ab landscape of the vaccinee can be overcome by increasing vaccine dose.
. 2022 Nov 15;209(10):1832-1836.
doi: 10.4049/jimmunol.2200577.
Cutting Edge: High-Dose Live Attenuated Influenza Vaccines Elicit Pulmonary Tissue-Resident Memory CD8+ T Cells in the Face of Pre-Existing Humoral Immunity
Ming Z M Zheng[SUP] 1 [/SUP], Svenja Fritzlar[SUP] 1 [/SUP], Zhongfang Wang[SUP] 1 2 [/SUP], Tiong Kit Tan[SUP] 3 [/SUP], Katherine Kedzierska[SUP] 1 [/SUP], Alain Townsend[SUP] 3 4 [/SUP], Patrick C Reading[SUP] 1 5 [/SUP], Linda M Wakim[SUP] 1 [/SUP]
Affiliations
- PMID: 36426954
- DOI: 10.4049/jimmunol.2200577
Abstract
In this study, we investigated how pre-existing Ab immunity to influenza virus established from prior immunizations affects the development of CD8+ T cell responses evoked after vaccination with a live attenuated vaccine. Using a mouse model and a panel of live attenuated influenza virus vaccine candidates (cold adapted and single cycle), we show that pre-existing influenza-specific Abs directed against the vaccine backbone attenuate the size and quality of the vaccine-induced CD8+ T cell response. Importantly, we show that increasing the vaccine dose can overcome this impediment, resulting in improved vaccine-induced circulating and tissue-resident memory CD8+ T cell responses, which were protective against heterologous influenza challenge. Thus, the reduced size and quality of the T cell response elicited by a live attenuated influenza virus vaccine imparted by the influenza-specific Ab landscape of the vaccinee can be overcome by increasing vaccine dose.