tetano
Editor, Senior Moderator
Immunity
. 2025 Mar 19:S1074-7613(25)00092-5.
doi: 10.1016/j.immuni.2025.02.025. Online ahead of print. Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins
Jenna J Guthmiller[SUP] 1 [/SUP], Linda Yu-Ling Lan[SUP] 2 [/SUP], Lei Li[SUP] 3 [/SUP], Yanbin Fu[SUP] 4 [/SUP], Sean A Nelson[SUP] 4 [/SUP], Carole Henry[SUP] 5 [/SUP], Christopher T Stamper[SUP] 2 [/SUP], Henry A Utset[SUP] 5 [/SUP], Alec W Freyn[SUP] 6 [/SUP], Julianna Han[SUP] 7 [/SUP], Olivia Stovicek[SUP] 5 [/SUP], Jiaolong Wang[SUP] 5 [/SUP], Nai-Ying Zheng[SUP] 3 [/SUP], Min Huang[SUP] 3 [/SUP], Haley L Dugan[SUP] 2 [/SUP], Micah E Tepora[SUP] 5 [/SUP], Xueyong Zhu[SUP] 7 [/SUP], Yao-Qing Chen[SUP] 5 [/SUP], Anna-Karin E Palm[SUP] 5 [/SUP], Dustin G Shaw[SUP] 2 [/SUP], Madhumathi Loganathan[SUP] 6 [/SUP], Benjamin F Francis[SUP] 6 [/SUP], Jiayi Sun[SUP] 4 [/SUP], Jordan Chervin[SUP] 4 [/SUP], Chloe Troxell[SUP] 4 [/SUP], Philip Meade[SUP] 6 [/SUP], Nancy H L Leung[SUP] 8 [/SUP], Sophie A Valkenburg[SUP] 9 [/SUP], Sarah Cobey[SUP] 10 [/SUP], Benjamin J Cowling[SUP] 11 [/SUP], Ian A Wilson[SUP] 12 [/SUP], Adolfo García-Sastre[SUP] 13 [/SUP], Raffael Nachbagauer[SUP] 6 [/SUP], Andrew B Ward[SUP] 7 [/SUP], Lynda Coughlan[SUP] 14 [/SUP], Florian Krammer[SUP] 15 [/SUP], Patrick C Wilson[SUP] 16 [/SUP]
Affiliations
In a phase 1 clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved hemagglutinin (HA) stalk domain as designed. Here, we determined the specificity, function, and subsets of B cells induced by cHA vaccination by pairing single-cell RNA sequencing and B cell receptor repertoire sequencing. We have shown that the cHA-inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell (MBC) phenotype against two broadly neutralizing epitopes in the stalk domain. The overall specificities of the acute plasmablast (PB) and MBC responses clonally overlapped, suggesting B cell convergence to these broadly protective epitopes. At 1 year post immunization, we identified that cHA vaccination reshaped the HA-specific MBC pool to enrich for stalk-binding B cells. Altogether, these data indicate the cHA vaccine induced robust and durable B cell responses against broadly protective epitopes of the HA stalk domain, in line with serological data.
Keywords: HA anchor epitope; HA stalk epitope; broadly neutralizing epitopes; chimeric hemagglutinin; durable B cell responses; influenza; next-generation influenza vaccine; universal influenza vaccine.
. 2025 Mar 19:S1074-7613(25)00092-5.
doi: 10.1016/j.immuni.2025.02.025. Online ahead of print. Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins
Jenna J Guthmiller[SUP] 1 [/SUP], Linda Yu-Ling Lan[SUP] 2 [/SUP], Lei Li[SUP] 3 [/SUP], Yanbin Fu[SUP] 4 [/SUP], Sean A Nelson[SUP] 4 [/SUP], Carole Henry[SUP] 5 [/SUP], Christopher T Stamper[SUP] 2 [/SUP], Henry A Utset[SUP] 5 [/SUP], Alec W Freyn[SUP] 6 [/SUP], Julianna Han[SUP] 7 [/SUP], Olivia Stovicek[SUP] 5 [/SUP], Jiaolong Wang[SUP] 5 [/SUP], Nai-Ying Zheng[SUP] 3 [/SUP], Min Huang[SUP] 3 [/SUP], Haley L Dugan[SUP] 2 [/SUP], Micah E Tepora[SUP] 5 [/SUP], Xueyong Zhu[SUP] 7 [/SUP], Yao-Qing Chen[SUP] 5 [/SUP], Anna-Karin E Palm[SUP] 5 [/SUP], Dustin G Shaw[SUP] 2 [/SUP], Madhumathi Loganathan[SUP] 6 [/SUP], Benjamin F Francis[SUP] 6 [/SUP], Jiayi Sun[SUP] 4 [/SUP], Jordan Chervin[SUP] 4 [/SUP], Chloe Troxell[SUP] 4 [/SUP], Philip Meade[SUP] 6 [/SUP], Nancy H L Leung[SUP] 8 [/SUP], Sophie A Valkenburg[SUP] 9 [/SUP], Sarah Cobey[SUP] 10 [/SUP], Benjamin J Cowling[SUP] 11 [/SUP], Ian A Wilson[SUP] 12 [/SUP], Adolfo García-Sastre[SUP] 13 [/SUP], Raffael Nachbagauer[SUP] 6 [/SUP], Andrew B Ward[SUP] 7 [/SUP], Lynda Coughlan[SUP] 14 [/SUP], Florian Krammer[SUP] 15 [/SUP], Patrick C Wilson[SUP] 16 [/SUP]
Affiliations
- PMID: 40132593
- DOI: 10.1016/j.immuni.2025.02.025
In a phase 1 clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved hemagglutinin (HA) stalk domain as designed. Here, we determined the specificity, function, and subsets of B cells induced by cHA vaccination by pairing single-cell RNA sequencing and B cell receptor repertoire sequencing. We have shown that the cHA-inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell (MBC) phenotype against two broadly neutralizing epitopes in the stalk domain. The overall specificities of the acute plasmablast (PB) and MBC responses clonally overlapped, suggesting B cell convergence to these broadly protective epitopes. At 1 year post immunization, we identified that cHA vaccination reshaped the HA-specific MBC pool to enrich for stalk-binding B cells. Altogether, these data indicate the cHA vaccine induced robust and durable B cell responses against broadly protective epitopes of the HA stalk domain, in line with serological data.
Keywords: HA anchor epitope; HA stalk epitope; broadly neutralizing epitopes; chimeric hemagglutinin; durable B cell responses; influenza; next-generation influenza vaccine; universal influenza vaccine.