Replicon particle vaccine protects swine against influenza

Bosworth, Brad T.; Erdman, Matthew M.; Stine, Douglas L.; Harris, Isabel Turney; Irwin, Christa; Milbradt, Jens; Loynachan, Alan T.; Kamrud, Kurt I.; Harris, D. L.

doi:10.1016/j.cimid.2010.05.002

Cited by 39 publications

(39 citation statements)

References 13 publications

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“…These efforts have been aimed at retargeting the host immune response and stimulating the production of broadly reactive antibodies against the HA and/or other viral proteins. Plasmid DNA (37)(38)(39)(40), recombinant adenoviruses (41-44), alphavirus replicon particles (45)(46)(47)(48), VLPs (49)(50)(51)(52)(53)(54)(55), and other methods have been used for influenza virus gene/protein delivery, alone or in combination. Among these methods, DNA vaccination offers many potential advantages-most notably, ease and low-cost production.…”

Section: Discussionmentioning

confidence: 99%

All-in-One Bacmids: an Efficient Reverse Genetics Strategy for Influenza A Virus Vaccines

Chen

Angel

et al. 2014

J Virol

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Vaccination is the first line of defense against influenza virus infection, yet influenza vaccine production methods are slow, antiquated, and expensive as a means to effectively reduce the virus burden during epidemic or pandemic periods. There is a great need for alternative influenza vaccines and vaccination methods with a global scale of impact. We demonstrate here a strategy to generate influenza A virus in vivo by using bacmid DNAs. Compared to the classical reverse genetics system, the "eight-in-one" bacmids (bcmd-RGFlu) showed higher efficiency of virus rescue in various cell types. Using a transfection-based inoculation (TBI) system, intranasal delivery to DBA/2J and BALB/c mice of bcmd-RGFlu plus 293T cells led to the generation of lethal PR8 virus in vivo. A prime-boost intranasal vaccination strategy using TBI in the context of a bcmd-RGFlu carrying a temperaturesensitive H1N1 virus resulted in protection of mice against lethal challenge with the PR8 strain. Taken together, these studies provide proof of principle to highlight the potential of vaccination against influenza virus by using in vivo reverse genetics. IMPORTANCEVaccination is the first line of defense against influenza virus infections. A major drawback in the preparation of influenza vaccines is that production relies on a heavily time-consuming process of growing the viruses in eggs. We propose a radical change in the way influenza vaccination is approached, in which a recombinant bacmid, a shuttle vector that can be propagated in both Escherichia coli and insect cells, carries an influenza virus infectious clone (bcmd-RGFlu). Using a surrogate cell system, we found that intranasal delivery of bcmd-RGFlu resulted in generation of influenza virus in mice. Furthermore, mice vaccinated with this system were protected against lethal influenza virus challenge. The study serves as a proof of principle of a potentially universal vaccine platform against influenza virus and other pathogens.

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Section: Discussionmentioning

confidence: 99%

All-in-One Bacmids: an Efficient Reverse Genetics Strategy for Influenza A Virus Vaccines

Chen

Angel

et al. 2014

J Virol

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“…Similarly, VEE-based expression of hemagglutinin (HA) elicited strong immune responses and even provided protection against challenges with H5N1 virus in chicken [36]. Likewise, expression of the swine influenza virus HA H3N2 gene from VEE vectors protected swine from influenza virus challenges [37]. In another study, the swine influenza HA gene was expressed from replication-deficient alphavirus particles showing no spread of vaccine or reversion to virulence in the intended host (pig) or non-host (mouse) species [38].…”

Section: Self-replicating Rna Virus-based Vaccinesmentioning

confidence: 99%

Replicon RNA Viral Vectors as Vaccines

Lundström¹

2016

Vaccines

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Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.

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“…Similarly, SFV particles expressing the HIV envelope [17] and gp41 [18] and VEE particles expressing HIV MA/CA [19] showed humoral and CTL (cytotoxic T-lymphocyte) responses in mice. Furthermore, a VEE particle vaccine expressing the cluster IV H3N2 swine influenza HA gene demonstrated protection against challenges with homologous influenza virus [20]. Likewise, mice and guinea pigs vaccinated with VEE particles expressing Ebola NP [21] and GP [22], respectively, provided protection against challenges with lethal doses of Ebola virus.…”

Section: Viral Vaccine Approachesmentioning

confidence: 99%

Alphavirus-Based Vaccines

Lundström¹

2014

Viruses

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Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.

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Replicon particle vaccine protects swine against influenza

Cited by 39 publications

References 13 publications

All-in-One Bacmids: an Efficient Reverse Genetics Strategy for Influenza A Virus Vaccines

All-in-One Bacmids: an Efficient Reverse Genetics Strategy for Influenza A Virus Vaccines

Replicon RNA Viral Vectors as Vaccines

Alphavirus-Based Vaccines

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