Correlated Studies of a Recombinant Influenza-Virus Vaccine. I. Derivation and Characterization of Virus and Vaccine

Kilbourne, Edwin D.; Schulman, Jerome L.; Schild, G. C.; Schloer, G. M.; Swanson, John; Bucher, Doris

doi:10.1093/infdis/124.5.449

Cited by 100 publications

(43 citation statements)

References 20 publications

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“…Thus, this platform is capable of generating protection against representative diseases from all three categories of the National Institute of Allergy and Infectious Diseases' Priority Pathogen List for emerging and rapidly increasing threats (52). Importantly, generation of a new MDNP vaccine system composed of these dendrimers and replicon RNA takes only about 1 wk, in contrast to the cell culture and fertilized egg systems that can take 6 mo or more to develop (53)(54)(55)(56)(57)(58). In addition, postproduction purification required for this MDNP system is minimal, as is the risk of contaminating allergens relative to existing vaccine systems (59)(60)(61).…”

Section: Significancementioning

confidence: 99%

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Chahal

Khan

Cooper

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

351

260

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Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

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Section: Significancementioning

confidence: 99%

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Chahal

Khan

Cooper

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

351

260

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“…X-99 was produced by reassortment of A/Shanghai/ 11/87 (Sh/87) and A/PR/8/34 (PR8) viruses by the usual procedure of dual infection of a chick embryo allantoic sac (Kilbourne et al, 1971). Viruses containing the HA and neuraminidase (NA) antigens of Sh/87 virus were isolated by passage with PR8 antibody.…”

Section: Derivation Of X-99 and X-99a Hy Reassortants From A/shanghaimentioning

confidence: 99%

Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants

Kilbourne

Johansson²,

Moran³

et al. 1993

Journal of General Virology

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“…This process, using gene reassortment, was first described in the 1960s (8) and occurs when an egg is infected with both the seasonal isolate and an egg-adapted highgrowth parent virus. Coinfected cells contain copies of both of the viral genomes, each comprising eight independent segments of viral RNA (vRNA), from which a range of viral progeny can potentially be packaged and released (9,10). Reassortant viruses containing the antigenic HA and NA of the seasonal strain are selected in the presence of antisera to the HA and NA of the egg-adapted strain.…”

mentioning

confidence: 99%

The Source of the PB1 Gene in Influenza Vaccine Reassortants Selectively Alters the Hemagglutinin Content of the Resulting Seed Virus

Cobbin

Verity

Gilbertson

et al. 2013

J Virol

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The yields of egg-grown influenza vaccines are maximized by the production of a seed strain using a reassortment of the seasonal influenza virus isolate with a highly egg-adapted strain. The seed virus is selected based on high yields of viral hemagglutinin (HA) and expression of the surface antigens from the seasonal isolate. The remaining proteins are usually derived from the highgrowth parent. However, a retrospective analysis of vaccine seeds revealed that the seasonal PB1 gene was selected in more than 50% of reassortment events. Using the model seasonal H3N2 virus A/Udorn/307/72 (Udorn) virus and the high-growth A/Puerto Rico/8/34 (PR8) virus, we assessed the influence of the source of the PB1 gene on virus growth and vaccine yield. Classical reassortment of these two strains led to the selection of viruses that predominantly had the Udorn PB1 gene. The presence of Udorn PB1 in the seed virus, however, did not result in higher yields of virus or HA compared to the yields in the corresponding seed virus with PR8 PB1. The 8-fold-fewer virions produced with the seed virus containing the Udorn PB1 were somewhat compensated for by a 4-fold increase in HA per virion. A higher HA/nucleoprotein (NP) ratio was found in past vaccine preparations when the seasonal PB1 was present, also indicative of a higher HA density in these vaccine viruses. As the HA viral RNA (vRNA) and mRNA levels in infected cells were similar, we propose that PB1 selectively alters the translation of viral mRNA. This study helps to explain the variability of vaccine seeds with respect to HA yield.

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Correlated Studies of a Recombinant Influenza-Virus Vaccine. I. Derivation and Characterization of Virus and Vaccine

Cited by 100 publications

References 20 publications

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants

The Source of the PB1 Gene in Influenza Vaccine Reassortants Selectively Alters the Hemagglutinin Content of the Resulting Seed Virus

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