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Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines.

ABSTRACT: Enveloped viruses enter cells by inducing fusion of viral and cellular membranes, a process catalyzed by a specialized membrane-fusion protein expressed on their surface. This review focuses on recent structural studies of viral fusion proteins with an emphasis on their metastable prefusion form and on interactions with neutralizing antibodies. The fusion glycoproteins have been difficult to study because they are present in a labile, metastable form at the surface of infectious virions. Such metastability is a functional requirement, allowing these proteins to refold into a lower energy conformation while transferring the difference in energy to catalyze the membrane fusion reaction. Structural studies have shown that stable immunogens presenting the same antigenic sites as the labile wild-type proteins efficiently elicit potently neutralizing antibodies, providing a framework with which to engineer the antigens for stability, as well as identifying key vulnerability sites that can be used in next-generation subunit vaccine design.

SUBMITTER: Rey FA

PROVIDER: S-EPMC7112304 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines.

Rey Felix A FA Lok Shee-Mei SM

Cell 20180301 6

Enveloped viruses enter cells by inducing fusion of viral and cellular membranes, a process catalyzed by a specialized membrane-fusion protein expressed on their surface. This review focuses on recent structural studies of viral fusion proteins with an emphasis on their metastable prefusion form and on interactions with neutralizing antibodies. The fusion glycoproteins have been difficult to study because they are present in a labile, metastable form at the surface of infectious virions. Such me ...[more]

PMID: 29522750

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Project description:Bluetongue (BT) is a haemorrhagic disease of wild and domestic ruminants with a huge economic worldwide impact on livestock. The disease is caused by BT-virus transmitted by Culicoides biting midges and disease control without vaccination is hardly possible. Vaccination is the most feasible and cost-effective way to minimize economic losses. Marketed BT vaccines are successfully used in different parts of the world. Inactivated BT vaccines are efficacious and safe but relatively expensive, whereas live-attenuated vaccines are efficacious and cheap but are unsafe because of under-attenuation, onward spread, reversion to virulence, and reassortment events. Both manufactured BT vaccines do not enable differentiating infected from vaccinated animals (DIVA) and protection is limited to the respective serotype. The ideal BT vaccine is a licensed, affordable, completely safe DIVA vaccine, that induces quick, lifelong, broad protection in all susceptible ruminant species. Promising vaccine candidates show improvement for one or more of these main vaccine standards. BTV protein vaccines and viral vector vaccines have DIVA potential depending on the selected BTV antigens, but are less effective and likely more costly per protected animal than current vaccines. Several vaccine platforms based on replicating BTV are applied for many serotypes by exchange of serotype dominant outer shell proteins. These platforms based on one BTV backbone result in attenuation or abortive virus replication and prevent disease by and spread of vaccine virus as well as reversion to virulence. These replicating BT vaccines induce humoral and T-cell mediated immune responses to all viral proteins except to one, which could enable DIVA tests. Most of these replicating vaccines can be produced similarly as currently marketed BT vaccines. All replicating vaccine platforms developed by reverse genetics are classified as genetic modified organisms. This implies extensive and expensive safety trails in target ruminant species, and acceptance by the community could be hindered. Nonetheless, several experimental BT vaccines show very promising improvements and could compete with marketed vaccines regarding their vaccine profile, but none of these next generation BT vaccines have been licensed yet.

Project description:All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of Spn. One of the most universal and comprehensive approaches of identifying novel vaccine candidates is the investigation of human sera from different disease stages of natural infections. Antigens that are robustly reactive in preliminary human serum screening constitute a pathogen-specific antigenome. This strategy has identified a number of Spn protein vaccine candidates that are moving forward in human clinical trials.

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Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines.

Publications

Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines.

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