title: Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.
abstract: Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Crina
authors.initials: C
authors.lastname: Stavaru
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Onu
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Emilia
authors.initials: E
authors.lastname: Lupulescu
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Tucureanu
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Orhan
authors.initials: O
authors.lastname: Rasid
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Ene
authors.initials: E
authors.lastname: Vlase
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Cristin
authors.initials: C
authors.lastname: Coman
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Caras
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghiorghisor
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Laurentiu
authors.initials: L
authors.lastname: Berbecila
authors.affiliation: a Cantacuzino National Research Institute , Bucharest , Romania.
authors.forename: Vlad
authors.initials: V
authors.lastname: Tofan
authors.affiliation: b Department of Biomedical Sciences , Colorado State University , Fort Collins , CO , USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bowen
authors.affiliation: b Department of Biomedical Sciences , Colorado State University , Fort Collins , CO , USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Marlenee
authors.affiliation: b Department of Biomedical Sciences , Colorado State University , Fort Collins , CO , USA.
authors.forename: Airn
authors.initials: A
authors.lastname: Hartwig
authors.affiliation: c Australian Infectious Diseases Research Centre, University of Queensland , Brisbane , Australia.
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.affiliation: d Infectious Disease Research Institute , Seattle , WA , USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Baldwin
authors.affiliation: d Infectious Disease Research Institute , Seattle , WA , USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Van Hoeven
authors.affiliation: d Infectious Disease Research Institute , Seattle , WA , USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Vedvick
authors.affiliation: e Biomedical Advanced Research and Development Authority, U.S. Dept of Health and Human Services , Washington, DC , USA.
authors.forename: Chuong
authors.initials: C
authors.lastname: Huynh
authors.affiliation: e Biomedical Advanced Research and Development Authority, U.S. Dept of Health and Human Services , Washington, DC , USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: O'Hara
authors.affiliation: f Southern Research Institute , Birmingham , AL , USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Noah
authors.affiliation: d Infectious Disease Research Institute , Seattle , WA , USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
mesh_terms: D000276:Adjuvants, Immunologic; D004353:Drug Evaluation, Preclinical; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D009821:Oils; D058873:Pandemics / Q000517:prevention & control; D012383:Romania; D018581:Technology Transfer; D014771:Virion / Q000502:physiology; D038301:Virus Inactivation
chemical_list: D000276:Adjuvants, Immunologic; D004655:Emulsions; D007252:Influenza Vaccines; D009821:Oils
keywords: oil-in-water emulsion; pandemic influenza; technology transfer; vaccine adjuvant; vaccine manufacturing