TY - JOUR
T1 - Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus
T2 - A Phase 1 dose-escalation study in healthy adults
AU - Cummings, James F.
AU - Guerrero, Melanie L.
AU - Moon, James E.
AU - Waterman, Paige
AU - Nielsen, Robin K.
AU - Jefferson, Stacie
AU - Gross, F. Liaini
AU - Hancock, Kathy
AU - Katz, Jacqueline M.
AU - Yusibov, Vidadi
AU - Chichester A., Jessica A.
AU - Jones, R. Mark
AU - Manceva D., Slobodanka D.
AU - Green J., Brian J.
AU - Stow, Mark
AU - Miao, Fudu
AU - Moonsammy, George
AU - Streatfield, Stephen J.
N1 - Funding Information:
The HAC1 clinical trial and serologic testing were supported by the Defense Advanced Research Projects Agency (DARPA) . The cGMP manufacture of HAC1 was supported by DARPA under contract number # HR0011-10-C-0051.
PY - 2014/4/17
Y1 - 2014/4/17
N2 - Background: Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). Methods: A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15μg, 45μg and 90μg) with and without Alhydrogel®, in healthy adults 18-50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). Results: The experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90. μg non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). Conclusions: This is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production.
AB - Background: Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). Methods: A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15μg, 45μg and 90μg) with and without Alhydrogel®, in healthy adults 18-50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). Results: The experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90. μg non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). Conclusions: This is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production.
KW - H1N1
KW - Hemagglutinin
KW - Influenza A
KW - Plant-produced
KW - Recombinant vaccine
UR - http://www.scopus.com/inward/record.url?scp=84897110525&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2013.10.017
DO - 10.1016/j.vaccine.2013.10.017
M3 - Article
C2 - 24126211
AN - SCOPUS:84897110525
SN - 0264-410X
VL - 32
SP - 2251
EP - 2259
JO - Vaccine
JF - Vaccine
IS - 19
ER -