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      Recombinant protein vaccines produced in insect cells

      review-article
      *
      Vaccine
      Elsevier Ltd.
      Baculovirus, Insect cells, Recombinant, Protein, Vaccine

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          Highlights

          ► BEVS has matured into a commercial manufacturing technology. ► A broad range of vaccines can be produced in a universal “plug and play” process. ► Vaccines can be produced at affordable prices. ► BEVS can offer sustainability of vaccine supply.

          Abstract

          The baculovirus-insect cell expression system is a well known tool for the production of complex proteins. The technology is also used for commercial manufacture of various veterinary and human vaccines. This review paper provides an overview of how this technology can be applied to produce a multitude of vaccine candidates.

          The key advantage of this recombinant protein manufacturing platform is that a universal “plug and play” process may be used for producing a broad range of protein-based prophylactic and therapeutic vaccines for both human and veterinary use while offering the potential for low manufacturing costs. Large scale mammalian cell culture facilities previously established for the manufacturing of monoclonal antibodies that have now become obsolete due to yield improvement could be deployed for the manufacturing of these vaccines. Alternatively, manufacturing capacity could be established in geographic regions that do not have any vaccine production capability. Dependent on health care priorities, different vaccines could be manufactured while maintaining the ability to rapidly convert to producing pandemic influenza vaccine when the need arises.

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          Most cited references72

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          Pneumococcal conjugate vaccine for childhood immunization--WHO position paper.

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            Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic.

            Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the viruses in cultured cells. For instance, it has not been established whether the major capsid protein L1 alone is sufficient for virus particle assembly. In addition, it is not known whether L1, L2 (the minor capsid protein), or both present the immunodominant epitopes required for induction of high-titer neutralizing antibodies. We have expressed the L1 major capsid proteins of bovine papillomavirus type 1 and human papillomavirus type 16 in insect cells via a baculovirus vector and analyzed their conformation and immunogenicity. The L1 proteins were expressed at high levels and assembled into structures that closely resembled papillomavirus virions. The self-assembled bovine papillomavirus L1, in contrast to L1 extracted from recombinant bacteria or denatured virions, also mimicked intact bovine papillomavirus virions in being able to induce high-titer neutralizing rabbit antisera. These results indicate that L1 protein has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent papillomavirus infection.
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              Expression, self-assembly, and antigenicity of the Norwalk virus capsid protein.

              Norwalk virus capsid protein was produced by expression of the second and third open reading frames of the Norwalk virus genome, using a cell-free translation system and baculovirus recombinants. Analysis of the expressed products showed that the second open reading frame encodes a protein with an apparent molecular weight of 58,000 (58K protein) and that this protein self-assembles to form empty viruslike particles similar to native capsids in size and appearance. The antigenicity of these particles was demonstrated by immunoprecipitation and enzyme-linked immunosorbent assays of paired serum samples from volunteers who developed illness following Norwalk virus challenge. These particles also induced high levels of Norwalk virus-specific serum antibody in laboratory animals following parenteral inoculation. A minor 34K protein was also found in infected insect cells. Amino acid sequence analysis of the N terminus of the 34K protein indicated that the 34K protein was a cleavage product of the 58K protein. The availability of large amounts of recombinant Norwalk virus particles will allow the development of rapid, sensitive, and reliable tests for the diagnosis of Norwalk virus infection as well as the implementation of structural studies.
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                Author and article information

                Contributors
                Journal
                Vaccine
                Vaccine
                Vaccine
                Elsevier Ltd.
                0264-410X
                1873-2518
                17 January 2012
                27 February 2012
                17 January 2012
                : 30
                : 10
                : 1759-1766
                Affiliations
                Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA
                Author notes
                [* ]Tel.: +1 203 686 0800; fax: +1 203 686 0268. manon.cox@ 123456proteinsciences.com
                Article
                S0264-410X(12)00031-X
                10.1016/j.vaccine.2012.01.016
                7115678
                22265860
                58e6642a-536c-49be-9066-8b0313591d6d
                Copyright © 2012 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 24 October 2011
                : 2 January 2012
                : 5 January 2012
                Categories
                Article

                Infectious disease & Microbiology
                baculovirus,insect cells,recombinant,protein,vaccine
                Infectious disease & Microbiology
                baculovirus, insect cells, recombinant, protein, vaccine

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