Invivac; influenza virus vaccine, inactivated, virosomal, cell cultured
Status: marketed in Europe
Cross ref.: See also other virosomal vaccines, Influenza vaccine, virosomal/Berna (Inflexal V) and Hepatitis A Virus Vaccine/Berna (Epaxal Berna). See the Influenza Vaccine Products entry.
Organizations involved:
Solvay S.A. – Manuf.; R&D; Tech.; Europe mark.
Abbive – Parent
Abbott Labs. – Former
Berna Biotech Ltd. – R&D; Tech.
Crucell N.V. – Parent
Swiss Serum and Vaccine Institute Berne – R&D; Tech.; Former
Description: Invivac is an aqueous trivalent formulation of inactivated influenza viruses (split-virus vaccine containing subunits), obtained from culture of the viruses in Madin-Darby canine kidney (MDCK) cells, adsorbed onto the surface of liposomal virosomes – immunopotentiating phospholipid membrane structures having two influenza virus antigens anchored in their membrane, hemagglutinin (HA) and neuraminidase (NA), with the structure essentially mimicking the influenza virus outer coat. Invivac is the first commercial cell culture-based influenza virus vaccine. Cultured viruses are inactivated with beta-propiolactone and purified.
Through the presence of the lecithin and the hemagglutinins, Immunopotentiating Reconstituted Influenza Virosomes (IRIVs) are formed. The virosomes form a fully biodegradable adjuvant that mimics natural virus. The influenza viral antigens hemagglutinin and neuraminidase are anchored into this lipid bilayer, with the virosome mimicking a natural influenza virus particle.
Nomenclature: Influenza vaccine, virosomal/Sanofi [BIO]; Invivac [TR]; influenza virus vaccine, inactivated, virosomal, cell cultured [SY]
Biological.: See the Inflexal V entry below for further information about virosomes, and how these liposomal membrane structures present influenza virus hemagglutinin on their surface, enabling them to attach and enter cells much the same as influenza virus.
Companies.: Invivac was developed, is manufactured and is marketed by Solvay S.A. Solvay constructed a new vaccine manufacturing facility in Weesp, Switzerland, which started-up in 2005.
Virosome technology originated with Berna Biotech Ltd., now merged into Crucell N.V. In April 1999, Berna and Solvay signed a license and distribution agreement to share expertise in the development of new vaccines for preventing influenza, and allowing both companies to develop and launch new influenza vaccines, with each company maintaining its own independent marketing. The pharmaceutical business of Solvay was acquired by Abbott Labs. for $6.6 billion in Sept. 2009. On Jan. 1, 2013, Abbott Labs. spun off its innovative pharmaceuticals business to Abbvie.
Solvay has formed a collaboration with Petrovax to develop new influenza vaccines in Russia.
Status: On June 24, 2004, Invivac received European Union (EU) approval through a Mutual Recognition Procedure (MRP). The Netherlands acted as the Reference Member State, with the vaccine’s first approvals granted in early 2004 in The Netherlands and Switzerland After the MRP, Norway and 13 EU member states granted a marketing authorization – Austria, Belgium, Denmark, Finland, Germany, Greece, Ireland, Italy, Luxembourg, Portugal, Spain, Sweden and the United Kingdom. For the other EU states, Solvay will start a repeat-use MRP in 2005. The vaccine is particularly targeted in the EU for use in the elderly. Invivac was launched for the 2004/5 flu season in Switzerland, The Netherlands, and UK. It was withdrawn from the U.K. market in Dec. 2006.
Tech. transfer: Virosome technology was licensed from Berna Biotech (now merged into Crucell N.V.). See the Inflexal V entry (#482) for further information. The Swiss Serum and Vaccine Institute Berne, now Berna Biotech (merged into Crucell N.V. in Jan. 2006), developed virosomal vaccine technology and has received patents, including U.S. 5,879,685, “Immunostimulating and im-munopotentiating reconstituted influenza virosomes and vaccines containing them.”
Trials: Clinical trials with Invivac were reviewed in Virus Research 2004 Jul;103(1-2):139-45. Invivac was studied in 14 trials in 2,865 subjects. The vaccine fully complies with the Committee for Proprietary Medicinal Products (CPMP), European Union, requirements for immunogenicity of influenza vaccines. The vaccine is especially efficacious in subjects with low pre-vaccination immunity, including the elderly. In a subset of subjects with low pre-vaccination titers (who most need protection by a vaccine), between 76-99% of subjects (dependent on age, health status and vaccine components) achieved protective hemagglutination inhibiting (HI) antibody titers after vaccination. Acceptable frequencies of well-known local and systemic reactions were observed in healthy adults and at-risk subjects in clinical studies, and in a post-marketing study population. These reactions were transient and generally not severe, and did not cause major inconvenience.
Index Terms:
Companies involvement:
Full monograph
483 Influenza vaccine, virosomal/Solvay
Nomenclature:
Influenza vaccine, virosomal/Sanofi [BIO]
Invivac [TR]
Influenza Virus Vaccine [FDA USAN]
influenza virus vaccine, inactivated, virosomal, cell cultured [SY]
FDA Class: Biologic BLA
Annual sales (2008, $millions) = $198
biopharmaceutical products
lipoproteins
vaccines, inactivated
vaccines, intranasal
vaccines, subunit
vaccines, viral
cancer, thyroid
influenza virus
keratinocytes, human
Mab 1129, murine monoclonal antibody
mammalian cell culture
virus culture
beta-propiolactone (BPL; beta propiolactone)
beta-propiolactone (BPL; beta propiolactone)
disodium hydrogen phosphate
hemagglutinin (HA) antigen, influenza A virus
influenza virus
influenza virus
Latrodectus mactans
lipoproteins
neuraminidase
phospholipases
potassium dihydrogen phosphate
sodium chloride
Sterile Water for Injection
viral inactivation, unspecified
North American coral snake
EU200 Currently Approved in EU
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM001 Marketed Product in EU
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