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 - 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 - https://www.scopus.com/pages/publications/85041487503
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 -