tetano
Editor, Senior Moderator
Cell Host Microbe
. 2021 Nov 10;S1931-3128(21)00473-X.
doi: 10.1016/j.chom.2021.10.009. Online ahead of print.
Human influenza virus challenge identifies cellular correlates of protection for oral vaccination
David R McIlwain[SUP] 1 [/SUP], Han Chen[SUP] 2 [/SUP], Zainab Rahil[SUP] 2 [/SUP], Neda Hajiakhoond Bidoki[SUP] 3 [/SUP], Sizun Jiang[SUP] 4 [/SUP], Zach Bjornson[SUP] 2 [/SUP], Nikita S Kolhatkar[SUP] 5 [/SUP], C Josefina Martinez[SUP] 5 [/SUP], Brice Gaudillière[SUP] 6 [/SUP], Julien Hedou[SUP] 6 [/SUP], Nilanjan Mukherjee[SUP] 2 [/SUP], Christian M Schürch[SUP] 7 [/SUP], Angelica Trejo[SUP] 2 [/SUP], Melton Affrime[SUP] 8 [/SUP], Bonnie Bock[SUP] 8 [/SUP], Kenneth Kim[SUP] 9 [/SUP], David Liebowitz[SUP] 5 [/SUP], Nima Aghaeepour[SUP] 10 [/SUP], Sean N Tucker[SUP] 5 [/SUP], Garry P Nolan[SUP] 11 [/SUP]
Affiliations
Abstract
Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4β7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.
Keywords: CyTOF; cellular immunity; correlates of protection; influenza challenge study; influenza vaccine; mass cytometry.
. 2021 Nov 10;S1931-3128(21)00473-X.
doi: 10.1016/j.chom.2021.10.009. Online ahead of print.
Human influenza virus challenge identifies cellular correlates of protection for oral vaccination
David R McIlwain[SUP] 1 [/SUP], Han Chen[SUP] 2 [/SUP], Zainab Rahil[SUP] 2 [/SUP], Neda Hajiakhoond Bidoki[SUP] 3 [/SUP], Sizun Jiang[SUP] 4 [/SUP], Zach Bjornson[SUP] 2 [/SUP], Nikita S Kolhatkar[SUP] 5 [/SUP], C Josefina Martinez[SUP] 5 [/SUP], Brice Gaudillière[SUP] 6 [/SUP], Julien Hedou[SUP] 6 [/SUP], Nilanjan Mukherjee[SUP] 2 [/SUP], Christian M Schürch[SUP] 7 [/SUP], Angelica Trejo[SUP] 2 [/SUP], Melton Affrime[SUP] 8 [/SUP], Bonnie Bock[SUP] 8 [/SUP], Kenneth Kim[SUP] 9 [/SUP], David Liebowitz[SUP] 5 [/SUP], Nima Aghaeepour[SUP] 10 [/SUP], Sean N Tucker[SUP] 5 [/SUP], Garry P Nolan[SUP] 11 [/SUP]
Affiliations
- PMID: 34784508
- DOI: 10.1016/j.chom.2021.10.009
Abstract
Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4β7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.
Keywords: CyTOF; cellular immunity; correlates of protection; influenza challenge study; influenza vaccine; mass cytometry.