Eleven years of Inflexal® V—a virosomal adjuvanted influenza vaccine

doi:10.1016/j.vaccine.2009.05.029

Vaccine

Volume 27, Issue 33, 16 July 2009, Pages 4381-4387

https://doi.org/10.1016/j.vaccine.2009.05.029 Get rights and content

Abstract

Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold over 41 million doses worldwide of the virosomal adjuvanted influenza vaccine, Inflexal^® V. Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal^® V have been completed in which 3920 subjects participated. During its decade on the market, Inflexal^® V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and its purity is reflected in the low ovalbumin content. By mimicking natural infection, the vaccine is highly efficacious. Inflexal^® V is the only adjuvanted influenza vaccine licensed for all age groups and shows a good immunogenicity in both healthy and immunocompromised elderly, adults and children. This review presents and discusses the experience with Inflexal^® V during the past decade.

Section snippets

Influenza viruses and epidemics

Influenza is one of the most important respiratory infections of humans, responsible for 300,000–500,000 annual deaths worldwide [1], [2]. The influenza viruses are capable of genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses [3]. Antigenic drift is the gradual evolution of viral strains, due to frequent mutations of the surface glycoproteins hemagglutinin and neuraminidase [4], [5]. Consequently, infecting viruses can no longer be

Impact of influenza vaccination on health economics

Louis Pasteur, who developed the first vaccine against rabies, established in 1881 the basic paradigm for vaccine development, which included the isolation, inactivation and injection of the causative pathogen. These basic principles have guided vaccine development during the twentieth century [13]. The use of whole virus influenza vaccines has discontinued, primarily due to the high level of reactogenicity associated. Influenza vaccines on the market are either split virus or subunit

Virosomes as an adjuvant system

Novel and increasingly safer vaccines use well-characterized antigens. However, these antigens are often too small to be highly immunogenic and would benefit from administration of a suitable adjuvant [26], [27], [28].

Virosomes demonstrate the characteristics of an adjuvant system and are biodegradable, non-toxic and do not induce antibodies against themselves [29]. The virosomes are reconstituted influenza virus envelopes devoid of inner core and genetic information. During the production

Immunogenicity of Inflexal^® V

Due to the virosomal technology, Inflexal^® V is highly efficacious by mimicking natural viral infection. The use of virosomes to deliver influenza antigens stimulates a strong immune response of immunocompetent cells [31], [35].

For influenza vaccines to be accepted throughout the European Union (EU), annual clinical trials must demonstrate immunogenicity and safety in at least 50 subjects between 18 and 60 years and in 50 subjects over 60 years. Vaccines must fulfil at least one of the three

Safety of Inflexal^® V

The purity and biocompatible nature of the virosomal constituents result in a significantly reduced rate of unwanted side effects as confirmed in a clinical study comparing a commercially available non-virosomal adjuvanted vaccine with Inflexal^® V [38].

Inflexal^® V contains no thiomersal or formaldehyde and is completely biodegradable. The purity of the vaccine is reflected in its low ovalbumin content, an indication of the amount of residual egg protein. In a survey of several influenza

Clinical experience with Inflexal^® V

Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal^® V have been completed in which 3920 subjects participated and 2205 subjects received the final formulation of Inflexal^® V. Of these, 906 were adults (18–60 years), 948 were elderly (>60 years), and 351 were children or adolescents (0.5 to <18 years). Two post-marketing surveillance studies including 1,127 adults and adolescents (>16 years) and 405 children (≥6 months to ≤6 years), respectively

Conclusion

Inflexal^® V is the only virosomal adjuvanted influenza vaccine licensed for all age groups. During its 11 years on the market, Inflexal^® V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and very low levels of ovalbumin. It is completely biodegradable and highly efficacious by mimicking natural infection. Inflexal^® V has a good immunogenicity in both healthy and immunocompromised elderly, adults and children.

Acknowledgement

We thank Marie Lovoll for her contribution in writing the manuscript.

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¹: Current address: Kenta Biotech AG, Rehhagstrasse 79, 3018 Berne, Switzerland.

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ReviewEleven years of Inflexal® V—a virosomal adjuvanted influenza vaccine

Abstract

Section snippets

Influenza viruses and epidemics

Impact of influenza vaccination on health economics

Virosomes as an adjuvant system

Immunogenicity of Inflexal® V

Safety of Inflexal® V

Clinical experience with Inflexal® V

Conclusion

Acknowledgement

Vaccine

Vaccine

Vaccine

FEBS Letters

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Current Opinion in Immunology

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Lancet

Seminars in Pediatric Infectious Diseases

Vaccine

Vaccine

Vaccine

Vaccine

Virology

Virus Research

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

The genomic and epidemiological dynamics of human influenza A virus

Nature

Antigenic drift in influenza virus H3 hemagglutinin from 1968 to 1980: multiple evolutionary pathways and sequential amino acid changes at key antigenic sites

Journal of Virology

Influenza vaccine—outmaneuvering antigenic shift and drift

New England Journal of Medicine

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

Nature

Influenza pandemics of the 20th century

Emerging Infectious Diseases

The global circulation of seasonal influenza A (H3N2) viruses

Science

Review
Eleven years of Inflexal^® V—a virosomal adjuvanted influenza vaccine

Immunogenicity of Inflexal^® V

Safety of Inflexal^® V

Clinical experience with Inflexal^® V