Abstract
Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal virus infection in mice. Whole inactivated virus-induced cross-protection was found to be mediated primarily by flu-specific CD8+ T cells. As it has been demonstrated that the route of vaccine administration strongly influences both the quantity and quality of vaccine-induced immunity, in this study, we determined which route of WIV administration induces optimal heterosubtypic cross-protection. We compared the magnitude of the immune response and heterosubtypic protection against lethal A/PR/8/34 (H1N1) infection after subcutaneous (SC), intramuscular (IM), and intranasal (IN) vaccination with A/NIBRG-14 (H5N1) WIV. Subcutaneous and IM administration was superior to IN administration of influenza WIV in terms of flu-specific CD8+ T-cell induction and protection of mice against lethal heterosubtypic challenge. Surprisingly, despite the very low flu-specific CD8+ T-cell responses detected in IN-vaccinated mice, these animals were partially protected, most likely due to cross-reactive IgA antibodies. The results of this study show that the magnitude of WIV-induced flu-specific CD8+ T-cell activity depends on the applied vaccination route. We conclude that parenteral administration of WIV vaccine, in particular IM injection, is superior to IN vaccine delivery for the induction of heterosubtypic cross-protection and generally appears to elicit stronger immune responses than mucosal vaccination with WIV.
Highlights
Annual influenza epidemics represent a major cause of morbidity and mortality worldwide.[1]
Heterosubtypic cross-protection induced by whole inactivated virus (WIV) administered through different vaccination routes
Seven days after the booster vaccination, mice were exposed to heterosubtypic challenge with 100 TCID50 of live Puerto Rico/8/34 (PR8) and monitored daily for body weight loss
Summary
Annual influenza epidemics represent a major cause of morbidity and mortality worldwide.[1]. The overall success of seasonal vaccination depends mainly on the antigenic match between the vaccine and the circulating virus strain and may vary substantially from one season to the next.[5,6] The antigenic composition of an emerging pandemic virus cannot be predicted at all, which makes it difficult to prepare sufficient vaccine stocks in due time.[6] To restrict the impact of “between-season” strain variability and to attenuate the threat of a pandemic influenza outbreak, cross-protective influenza vaccines are desirable Such vaccines should ideally target conserved viral antigens, such as the internal nucleoprotein (NP) or the matrix protein (M1).[7,8]. Whole inactivated virus-induced cross-protection was found to be mediated primarily by flu-specific CD8+ T cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
