tetano
Editor, Senior Moderator
Nat Commun
. 2026 Apr 13;17(1):3451.
doi: 10.1038/s41467-026-70396-1.
A group 1 hemagglutinin stem vaccine elicits broad humoral responses against influenza in phase 1/2a study
Nina Hertoghs[SUP] #[/SUP][SUP] 1 [/SUP], Chan Tang[SUP] #[/SUP][SUP] 1 [/SUP], Vitalija van Paassen[SUP] 1 [/SUP], Mandy Jongeneelen[SUP] 1 2 [/SUP], Jeroen Tolboom[SUP] 1 [/SUP], Lynn Yieh[SUP] 1 [/SUP], Miao Wang[SUP] 1 [/SUP], Krisztian Kaszas[SUP] 1 [/SUP], Chelsea McLean[SUP] 1 [/SUP], Sara van den Berg[SUP] 1 3 [/SUP], David Lowson[SUP] 1 4 [/SUP], Weihong Hu[SUP] 1 4 [/SUP], Zuleima Aguilar[SUP] 1 [/SUP], Jenny Hendriks[SUP] 1 5 [/SUP], Harmjan Kuipers[SUP] 1 [/SUP], Sarah Kulke[SUP] 1 [/SUP], Jerald Sadoff[SUP] 1 6 [/SUP], Boerries Brandenburg[SUP] 1 [/SUP], Roland Zahn[SUP] 7 [/SUP]
Affiliations
Vaccines targeting the conserved stem region of influenza hemagglutinin (HA) may induce broad immunity and reduce reliance on strain-matched seasonal formulations. This Phase 1/2a study evaluates safety and immunogenicity of a universal influenza vaccine component comprising a soluble trimeric stabilized group 1 HA-stem protein (INFLUENZA G1 mHA). Healthy adults aged 18-to-45 received one or two doses at 45 µg or 135 µg, with or without Al(OH)₃. Primary endpoints were safety and reactogenicity. All regimens were well-tolerated with no vaccine-related serious adverse events. Secondary and exploratory endpoints included binding, neutralizing, and ADCC responses compared to a matched quadrivalent seasonal influenza vaccine cohort. A single dose induced robust binding antibody responses to H5 HA and homologous stem HA, with 6.5-16.4-fold increases at Day 29 versus baseline, exceeding responses elicited by the seasonal influenza vaccine. Additionally, we demonstrate broader binding to a panel of group 1 HAs, with responses maintained for at least one year. Neutralizing antibody and ADCC responses at Day 29 showed 7.9-15-fold and 4.9-8.6-fold increases, respectively. Importantly, serum from vaccinated participants protect mice against lethal heterologous H5N1 challenge. This study provides proof of concept that the HA stem vaccine elicits broad and durable influenza A group 1-directed immunity. This trial is registered with ClinicalTrials.gov (NCT05901636).
. 2026 Apr 13;17(1):3451.
doi: 10.1038/s41467-026-70396-1.
A group 1 hemagglutinin stem vaccine elicits broad humoral responses against influenza in phase 1/2a study
Nina Hertoghs[SUP] #[/SUP][SUP] 1 [/SUP], Chan Tang[SUP] #[/SUP][SUP] 1 [/SUP], Vitalija van Paassen[SUP] 1 [/SUP], Mandy Jongeneelen[SUP] 1 2 [/SUP], Jeroen Tolboom[SUP] 1 [/SUP], Lynn Yieh[SUP] 1 [/SUP], Miao Wang[SUP] 1 [/SUP], Krisztian Kaszas[SUP] 1 [/SUP], Chelsea McLean[SUP] 1 [/SUP], Sara van den Berg[SUP] 1 3 [/SUP], David Lowson[SUP] 1 4 [/SUP], Weihong Hu[SUP] 1 4 [/SUP], Zuleima Aguilar[SUP] 1 [/SUP], Jenny Hendriks[SUP] 1 5 [/SUP], Harmjan Kuipers[SUP] 1 [/SUP], Sarah Kulke[SUP] 1 [/SUP], Jerald Sadoff[SUP] 1 6 [/SUP], Boerries Brandenburg[SUP] 1 [/SUP], Roland Zahn[SUP] 7 [/SUP]
Affiliations
- PMID: 41974675
- DOI: 10.1038/s41467-026-70396-1
Vaccines targeting the conserved stem region of influenza hemagglutinin (HA) may induce broad immunity and reduce reliance on strain-matched seasonal formulations. This Phase 1/2a study evaluates safety and immunogenicity of a universal influenza vaccine component comprising a soluble trimeric stabilized group 1 HA-stem protein (INFLUENZA G1 mHA). Healthy adults aged 18-to-45 received one or two doses at 45 µg or 135 µg, with or without Al(OH)₃. Primary endpoints were safety and reactogenicity. All regimens were well-tolerated with no vaccine-related serious adverse events. Secondary and exploratory endpoints included binding, neutralizing, and ADCC responses compared to a matched quadrivalent seasonal influenza vaccine cohort. A single dose induced robust binding antibody responses to H5 HA and homologous stem HA, with 6.5-16.4-fold increases at Day 29 versus baseline, exceeding responses elicited by the seasonal influenza vaccine. Additionally, we demonstrate broader binding to a panel of group 1 HAs, with responses maintained for at least one year. Neutralizing antibody and ADCC responses at Day 29 showed 7.9-15-fold and 4.9-8.6-fold increases, respectively. Importantly, serum from vaccinated participants protect mice against lethal heterologous H5N1 challenge. This study provides proof of concept that the HA stem vaccine elicits broad and durable influenza A group 1-directed immunity. This trial is registered with ClinicalTrials.gov (NCT05901636).