History of RA27/3 Rubella Vaccine

Plotkin, Stanley А.; Buser, F.

doi:10.1093/clinids/7.supplement_1.s77

Cited by 28 publications

(9 citation statements)

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“…Cold-adaptation (adaptation to growth at low (<37°C) temperature by serial passage) is often associated with reduced replication (or sensitivity) at higher temperatures (37–40°C)). Historically, cold-adaptation has been frequently used to generate attenuated RNA and DNA viruses (reviewed in [ 27 ]), including influenza [ 28 , 29 ], measles [ 30 ], and rubella vaccine strains [ 31 ]. Cold-adapted polioviruses have also been generated in the past by passage at 23–30°C [ 32 – 34 ].…”

Section: Introductionmentioning

confidence: 99%

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

et al. 2016

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The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive PER.C6 cell culture platform, the stably attenuated CAVA strains may serve as an attractive low-cost and (bio)safe option for the production of a novel next generation IPV.

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Section: Introductionmentioning

confidence: 99%

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

et al. 2016

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“…[10][11][12] Data concerning persistence of antibodies after vaccination are somewhat variable, but the majority of studies show maintenance of positive antibodies for at least 20 years. [13][14][15] A second dose of rubella vaccine at 4-12 years of age is routinely recommended in many developed countries, not only primarily to immunize the few primary vaccine failures but also to provide a booster to those whose titers have fallen to low levels. 16,17 The most successful experience with rubella vaccination has been accumulated in Scandinavia, notably Sweden and Finland.…”

Section: Discussionmentioning

confidence: 99%

Rubella outbreak on Tokunoshima Island in 2004: Serological and epidemiological analysis of pregnant women with rubella

Kaneko

Sameshima

Ikenoue

et al. 2006

J of Obstet and Gynaecol

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“…Some variation was found between wt+ isolates but the most notable differences were found between the vaccine strains RA27/3 and Cendehill and wt+ isolates, particularly in yield, temperature sensitivity and in the pattern of glycosylation of El and E2 polypeptides demon strated on immunoblots. The temperature sensi tivity of RA27/3 and Cendehill is not surprising considering that these strains were cold-adapted during attenuation in WI-38 cells at 30°C for RA27/3 [36] or in primary rabbit kidney at 28°C in the case of Cendehill [37]. Even at 37°C, the growth characteristics of both RA27/3 and Cen dehill appear to be modified with virus yields considerably lower than found with wt+ strains or the old vaccine strain HPV77/DE5.…”

Section: Discussionmentioning

confidence: 99%

“…Only the Japanese vaccine To336 [24] appears to be less arthritogenic, while stimulating an equivalent im mune response in vaccine recipients [39]. The RA27/3 vaccine is also reported to be less teratogenic than other rubella strains, which is interesting considering that it was originally isolated from the kidney of a rubella-infected fetus [36]. Perhaps this relates to the greatly reduced ability of RA27/3 to infect PBMC reported here which may restrict dissemination of the virus throughout the body.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Rubella Virus Strain Differences Associated with Attenuation

Chantler¹,

Lund²,

Miki³

et al. 1993

Intervirology

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A comparison of the phenotypic properties of three rubella vaccines (HPV77/DE5, RA27/3 and Cendehill) and four wild-type (wt⁺) isolates (M33, Therien, Thomas and IB2) has been carried out. Differences in growth characteristics, plaque morphology and temperature sensitivity were identified. In addition differential reactivity of the strains to polyclonal and a monoclonal anti-E1 antibody were found in immunoperoxidase-staining reactions. The ability of the wt⁺ and vaccine strains to infect lymphoreticular cells and chondrocytes, also varied in that the RA27/3 and Cendehill strains were highly restricted in both these cell types while the wt⁺ strains and HPV77/DE5 vaccine grew to high titer. This biological variation was associated with differences in E1 and E2 glycoproteins detected on immunoblots.

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History of RA27/3 Rubella Vaccine

Cited by 28 publications

References 0 publications

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

Rubella outbreak on Tokunoshima Island in 2004: Serological and epidemiological analysis of pregnant women with rubella

Characterization of Rubella Virus Strain Differences Associated with Attenuation

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