TY - JOUR
T1 - An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades
T2 - a phase I trial
AU - Deming, Meagan E.
AU - Toapanta, Franklin R.
AU - Pasetti, Marcela
AU - Golding, Hana
AU - Khurana, Surender
AU - Hamouda, Tarek
AU - Fattom, Ali
AU - Liang, Yuanyuan
AU - Tennant, Sharon M.
AU - McGilvray, Megan F.
AU - Bernal, Paula J.
AU - Oshinsky, Jennifer J.
AU - Datta, Shrimati
AU - Booth, Jasnehta Permala
AU - Coughlan, Lynda
AU - Neuzil, Kathleen M.
AU - Costley, Chad D.
AU - Kotloff, Karen L.
AU - Sztein, Marcelo B.
AU - Ortiz, Justin R.
AU - Smith, Douglas M.
AU - Schneider, Cosette G.
AU - Rapaka, Rekha R.
AU - Posadas, Olivia
AU - Nkeze, Joseph N.
AU - Mishra, Ashish K.
AU - Manischewitz, Jody
AU - King, Lisa R.
AU - Kang, Insung
AU - Johnson-Mayo, Ifayet P.L.
AU - Hu, Jingping
AU - Campbell, James D.
AU - Agrawal, Vaidehi
AU - Acosta, Hugo
AU - On behalf of the rH5 Writing Group, behalf of the rH5 Writing Group
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Mucosal influenza vaccines may provide improved protection against infection and transmission, but their development is hindered by absence of immune correlates of protection. Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W805EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are minimal. However, adjuvanted H5 recipients show significant increases in mucosal and serum IgG/IgA, surface plasmon resonance antibody binding, memory B and CD4 T cell activity, and antibody-dependent cell-mediated cytotoxicity. Following H5N1 boost, participants mount robust responses across measurements and have microneutralization responses against diverse H5N1 clades (including circulating clade 2.3.4.4b). Findings demonstrate successful mucosal priming and broad cross-clade responses. This intranasal vaccine supports further exploration of mucosal immune biomarkers and may accelerate development of intranasal influenza vaccines. ClinicalTrials.gov
AB - Mucosal influenza vaccines may provide improved protection against infection and transmission, but their development is hindered by absence of immune correlates of protection. Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W805EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are minimal. However, adjuvanted H5 recipients show significant increases in mucosal and serum IgG/IgA, surface plasmon resonance antibody binding, memory B and CD4 T cell activity, and antibody-dependent cell-mediated cytotoxicity. Following H5N1 boost, participants mount robust responses across measurements and have microneutralization responses against diverse H5N1 clades (including circulating clade 2.3.4.4b). Findings demonstrate successful mucosal priming and broad cross-clade responses. This intranasal vaccine supports further exploration of mucosal immune biomarkers and may accelerate development of intranasal influenza vaccines. ClinicalTrials.gov
UR - https://www.scopus.com/pages/publications/105021077001
U2 - 10.1038/s41467-025-64686-3
DO - 10.1038/s41467-025-64686-3
M3 - Article
C2 - 41198655
AN - SCOPUS:105021077001
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 9321
ER -