Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine
Authors: Casazza Joseph P. , Hofstetter Amelia R. , Costner Pamela J. M. , Holman LaSonji A. , Hendel Cynthia S. , Widge Alicia T. , Wu Richard L. , Whalen William R. , Cunningham Jennifer , Arthur Anita , Wang Xiaolin , Ola Abidemi , Saunders Jamie , Mendoza Floreliz , Novik Laura , Burgos Florez Maria C. , Ortega-Villa Ana M. , Apte Preeti J. , Strom Larisa , Wang Lu , Imam Marjaan , Basappa Manjula , Naisan Mursal , Castro Mike , Trost Jessica F. , Narpala Sandeep R. , Vanderven Hillary A. , Yamshchikov Galina V. , Berkowitz Nina M. , Gordon Ingelise J. , Plummer Sarah H. , Wycuff Diane L. , Vazquez Sandra , Gillespie Rebecca A. , Creanga Adrian , Adams William C. , Carlton Kevin , Gall Jason G. , McDermott Adrian B. , Serebryannyy Leonid A. , Houser Katherine V. , Koup Richard A. , Graham Barney S. , Ledgerwood Julie E. , Mascola John R. , Pierson Theodore C. , Andrews Sarah F. , Kanekiyo Masaru , Dropulic Lesia K. ,   The VRC 323 study team, Abrah Akuah , Awan Seemal F. , Amoa-Awua Obrimpong , Apgar Martin , Beck Allison , Brooks Katherine , Bruington Tommy , Burch Eugenia , Case Chris , Coates Emily E. , Coe Erykah , Eshun Aba M. , Gaudinski Martin R. , Dyer Renunda , Le Lam , Larkin Brenda , Misasi John , Morgan Patricia , Mueller Allen , Nguyen Thuy , O’Callahan Mark , Ourahmane Amine , Parker Karen M. , Pittman Iris , Reiber Matthew , Requilman LaShawn , Shimberg Geoffrey , Silva Rosa , Stein Judy , Telscher Shinyi , Thillainathan Jagada , Vasilenko Olga , Chen Mingzhong , Chalamalasetty Naga , Chen Peifeng , Boonyaratanakornkit Bobby , Luedtke Robin , Leach Kristin , Arias Gabriel , Pratt Michael , Gulla Krishana , Gowetski Daniel B. , Holland-Linn Janel , Stephens Leigh Anne , Lei Paula , Bahorich Jessica , Cooper Jonathan , Yang Yanhong , Wang Eric , Shadrick William , Kueltzo Lisa , Banappagari Sashikanth , Albright Gabriela , Dobrescu Gelu , Nugent Sean , Moxey Gabriel , Chaudhuri Rajoshi 
Published: September 2024

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.