tetano
Editor, Senior Moderator
J Infect Dis
. 2020 Nov 27;jiaa728.
doi: 10.1093/infdis/jiaa728. Online ahead of print.
An R848 conjugated influenza virus vaccine elicits robust IgG to hemagglutinin stem in a newborn nonhuman primate model
Elene A Clemens[SUP] 1 [/SUP], Beth C Holbrook[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 2 [/SUP], Jonathan W Yewdell[SUP] 3 [/SUP], Barney S Graham[SUP] 2 [/SUP], Martha A Alexander-Miller[SUP] 1 [/SUP]
Affiliations
Abstract
Eliciting broadly protective antibodies is a critical goal for the development of more effective vaccines against influenza. Optimizing protection is of particular importance in newborns, who are highly vulnerable to severe disease following infection. An effective vaccination strategy for this population must surmount the challenges associated with the neonatal immune system as well as mitigate the inherent immune subdominance of conserved influenza virus epitopes, responses to which can provide broader protection. Here, we show that prime-boost vaccination with a TLR7/8 agonist (R848)-conjugated influenza A virus (IAV) vaccine elicits antibody responses to the highly conserved hemagglutinin stem and promotes rapid induction of virus neutralizing stem-specific antibodies following viral challenge. These findings support the efficacy of R848 as an effective adjuvant for newborns and demonstrate its ability to enhance antibody responses to subdominant antigenic sites in this at-risk population.
Keywords: HA stem; NHP; adjuvant; antibody; influenza vaccine; newborns; universal vaccine.
. 2020 Nov 27;jiaa728.
doi: 10.1093/infdis/jiaa728. Online ahead of print.
An R848 conjugated influenza virus vaccine elicits robust IgG to hemagglutinin stem in a newborn nonhuman primate model
Elene A Clemens[SUP] 1 [/SUP], Beth C Holbrook[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 2 [/SUP], Jonathan W Yewdell[SUP] 3 [/SUP], Barney S Graham[SUP] 2 [/SUP], Martha A Alexander-Miller[SUP] 1 [/SUP]
Affiliations
- PMID: 33245745
- DOI: 10.1093/infdis/jiaa728
Abstract
Eliciting broadly protective antibodies is a critical goal for the development of more effective vaccines against influenza. Optimizing protection is of particular importance in newborns, who are highly vulnerable to severe disease following infection. An effective vaccination strategy for this population must surmount the challenges associated with the neonatal immune system as well as mitigate the inherent immune subdominance of conserved influenza virus epitopes, responses to which can provide broader protection. Here, we show that prime-boost vaccination with a TLR7/8 agonist (R848)-conjugated influenza A virus (IAV) vaccine elicits antibody responses to the highly conserved hemagglutinin stem and promotes rapid induction of virus neutralizing stem-specific antibodies following viral challenge. These findings support the efficacy of R848 as an effective adjuvant for newborns and demonstrate its ability to enhance antibody responses to subdominant antigenic sites in this at-risk population.
Keywords: HA stem; NHP; adjuvant; antibody; influenza vaccine; newborns; universal vaccine.