tetano
Editor, Senior Moderator
Sci Transl Med
. 2025 Aug 6;17(810):eadt1452.
doi: 10.1126/scitranslmed.adt1452. Epub 2025 Aug 6. Nasal and systemic immune responses correlate with viral shedding after influenza challenge in people with complex preexisting immunity
Kathie-Anne Walters[SUP] 1 [/SUP], Charles A Blatti 3rd[SUP] 2 [/SUP], Ruoqing Zhu[SUP] 3 [/SUP], Barbara Banbury[SUP] 4 [/SUP], Luca T Giurgea[SUP] 5 [/SUP], Rachel Bean[SUP] 5 [/SUP], Eugene Han[SUP] 3 [/SUP], Yuhan Li[SUP] 3 [/SUP], Kelsey Scherler[SUP] 1 [/SUP], Jenna Sherry[SUP] 6 [/SUP], Sarah Formentini[SUP] 3 [/SUP], Wenzhuo Zhou[SUP] 3 [/SUP], Adriana Cervantes-Medina[SUP] 5 [/SUP], Monica Gouzoulis[SUP] 5 [/SUP], Luz Angela Rosas[SUP] 6 [/SUP], Alison Han[SUP] 5 [/SUP], Lisa Gatzke[SUP] 2 [/SUP], Colleen Bushell[SUP] 2 [/SUP], Ned Sherry[SUP] 4 [/SUP], Jeffery K Taubenberger[SUP] 6 [/SUP], Matthew J Memoli[SUP] 5 [/SUP], John C Kash[SUP] 6 [/SUP]
Affiliations
Each year in the United States, ~50% of adults ≥18 years old are vaccinated against influenza viruses, with protective efficacy averaging 40.5% over the past 20 years. To model annual seasonal influenza, a cohort of 74 adults, who were unscreened for preexisting A/H1N1 immunity and half of whom were recently immunized with licensed QIV (mean of 64 days), were challenged with A/H1N1 influenza virus. Transcriptomic, proteomic, and VDJ repertoire analyses were performed on nasal and peripheral blood samples from participants to identify nasal mucosal and systemic immune responses that correlated with viral shedding and immune correlates of protection. Viral-shedding participants showed increased T cell, but not B cell, VDJ diversity with expansion of low-frequency B cell clones postchallenge, including broadly neutralizing motifs. Nonshedding participants demonstrated decreased clonality and increased richness of B and T cell VDJ clones, increased preinoculation nasal mucosal immune gene and serum protein expression, and increased ex vivo peripheral blood mononuclear cell responses. Nasal mucosal responses in participants shedding virus for 2 or more days showed higher early viral loads and exhibited stronger induction of antiviral responses compared with those in participants who shed virus for 1 day. Last, participants with a single day of viral shedding were three times more likely to be female. These data shed light on the complex immune responses in the nasal mucosa and the periphery after influenza vaccination and infection, which will be critical for next-generation vaccine development.
. 2025 Aug 6;17(810):eadt1452.
doi: 10.1126/scitranslmed.adt1452. Epub 2025 Aug 6. Nasal and systemic immune responses correlate with viral shedding after influenza challenge in people with complex preexisting immunity
Kathie-Anne Walters[SUP] 1 [/SUP], Charles A Blatti 3rd[SUP] 2 [/SUP], Ruoqing Zhu[SUP] 3 [/SUP], Barbara Banbury[SUP] 4 [/SUP], Luca T Giurgea[SUP] 5 [/SUP], Rachel Bean[SUP] 5 [/SUP], Eugene Han[SUP] 3 [/SUP], Yuhan Li[SUP] 3 [/SUP], Kelsey Scherler[SUP] 1 [/SUP], Jenna Sherry[SUP] 6 [/SUP], Sarah Formentini[SUP] 3 [/SUP], Wenzhuo Zhou[SUP] 3 [/SUP], Adriana Cervantes-Medina[SUP] 5 [/SUP], Monica Gouzoulis[SUP] 5 [/SUP], Luz Angela Rosas[SUP] 6 [/SUP], Alison Han[SUP] 5 [/SUP], Lisa Gatzke[SUP] 2 [/SUP], Colleen Bushell[SUP] 2 [/SUP], Ned Sherry[SUP] 4 [/SUP], Jeffery K Taubenberger[SUP] 6 [/SUP], Matthew J Memoli[SUP] 5 [/SUP], John C Kash[SUP] 6 [/SUP]
Affiliations
- PMID: 40768601
- DOI: 10.1126/scitranslmed.adt1452
Each year in the United States, ~50% of adults ≥18 years old are vaccinated against influenza viruses, with protective efficacy averaging 40.5% over the past 20 years. To model annual seasonal influenza, a cohort of 74 adults, who were unscreened for preexisting A/H1N1 immunity and half of whom were recently immunized with licensed QIV (mean of 64 days), were challenged with A/H1N1 influenza virus. Transcriptomic, proteomic, and VDJ repertoire analyses were performed on nasal and peripheral blood samples from participants to identify nasal mucosal and systemic immune responses that correlated with viral shedding and immune correlates of protection. Viral-shedding participants showed increased T cell, but not B cell, VDJ diversity with expansion of low-frequency B cell clones postchallenge, including broadly neutralizing motifs. Nonshedding participants demonstrated decreased clonality and increased richness of B and T cell VDJ clones, increased preinoculation nasal mucosal immune gene and serum protein expression, and increased ex vivo peripheral blood mononuclear cell responses. Nasal mucosal responses in participants shedding virus for 2 or more days showed higher early viral loads and exhibited stronger induction of antiviral responses compared with those in participants who shed virus for 1 day. Last, participants with a single day of viral shedding were three times more likely to be female. These data shed light on the complex immune responses in the nasal mucosa and the periphery after influenza vaccination and infection, which will be critical for next-generation vaccine development.