TY - JOUR
T1 - A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies
AU - Nachbagauer, Raffael
AU - Liu, Wen Chun
AU - Choi, Angela
AU - Wohlbold, Teddy John
AU - Atlas, Talia
AU - Rajendran, Madhusudan
AU - Solórzano, Alicia
AU - Berlanda-Scorza, Francesco
AU - Garciá-Sastre, Adolfo
AU - Palese, Peter
AU - Albrecht, Randy A.
AU - Krammer, Florian
N1 - Funding Information:
We thank Bruce L. Innis, Nicolas Lecrenier and Corey Mallett at GlaxoSmithKline for providing AS03 and split virion antigen. We also thank Larisa Rudenko and Irina Isakova-Sivak at the Institute of Experimental Medicine (St. Petersburg, Russia) for their help with the LAIV backbone selection, David Wentworth at the CDC for rescuing the cH8/1 LAIV virus and David Suarez at the USDA for virus pathotyping. Furthermore, we thank the team at PATH for help with the coordination of the project. This publication is based on research funded in part by the Bill & Melinda Gates Foundation (OPP1084518), NIAID grants U19 AI109946 and P01AI097092, the Centers of Influenza Virus Research and Surveillance (CEIRS) contract HHSN272201400008C, the Biomedical Advanced Research and Development Authority (BARDA, HHSO100201500010C) and PATH (GAT.1878-01162340-COL). WCL is a recipient of a training fellowship from the Taiwan Ministry of Science and Technology (MOST 105-2917-I-564 -006 -A1). GlaxoSmithKline contributed cH5/1 and cH8/1 split vaccines as well as AS03 for the study. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the funders.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.
AB - Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.
UR - http://www.scopus.com/inward/record.url?scp=85041487503&partnerID=8YFLogxK
U2 - 10.1038/s41541-017-0026-4
DO - 10.1038/s41541-017-0026-4
M3 - Article
AN - SCOPUS:85041487503
SN - 2059-0105
VL - 2
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 26
ER -