Clinical Trials With a Live Attenuated Rubella Virus Vaccine

Abstract

IN VITRO and in vivo properties of the attenuated Cendehill strain of rubella virus have been described previously. This strain has been attenuated by serial propagation in primary rabbit kidney cells. It is characterized by the production of an early cytopathic effect in rabbit cultures, by the formation of distinct plaques in RK13 cells, by loss of intranasal infectivity for the monkey, and by loss of immunogenicity for the rabbit after subcutaneous inoculation.1,2 Preliminary clinical trials with the Cendehill strain at the 21st and 51st passage levels have been reported previously.3-6Although attenuated virus at the 21st passage failed to spread from vaccinated subjects to susceptible contacts, the trials with this passage level were discontinued because mild but typical symptoms of rubella were observed in one of the vaccinees.4 We report here the results of several clinical trials in children and young adults, with the high-passage level (51st) Cendehill strain.

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

“…When we have emulated the original approach, and used replication-competent viruses as the immunogen, we have succeeded in preventing yellow fever, poliomyelitis, mumps, measles, rubella, chickenpox, and shingles [67], [68], [69], [70], [71], [72]. In the past 30 years, research into live-attenuated viral vaccines has been largely replaced with research into viral subunit vaccines.…”

“…We will be interested to learn if this observation is unique to HSV-2 or applies to other viruses. In principle, one means to test this hypothesis would be to compare the efficacy of immunization with one of the live viruses used in childhood vaccines (i.e., varicella-zoster virus [VZV] Oka strain [68], measles virus Schwarz strain [69], mumps virus Jeryl Linn strain [70], or rubella virus Cendehill strain [71]) relative to immunization with a protein subunit derived from the same virus.…”

“…Hence, studies are in progress to compare the efficacy of the HSV-2 0ΔNLS vaccine strain relative to a replication-defective HSV-2 virus, similar in principle to Sanofi Pasteur's lead HSV-2 vaccine candidate, ACAM-529 [23], [24], [25]. We conclude by noting that while live viruses, such as HSV-2 0ΔNLS, are the basis of ∼75% of our effective viral vaccines [67], [68], [69], [70], [71], [72], there is not a single vaccine in clinical use that contains a replication-defective virus.…”

“…The live viral vaccines used in clinical practice today were developed between 1940 and 1975 [67], [68], [69], [70], [71], [72], and rely on single-nucleotide substitutions for their attenuated phenotype [84], [85]. We propose that genetic engineering could be applied to derive a 2 nd generation of live-attenuated viruses that are equally effective, but which are safer (more stable) due to large, in-frame deletions that are unable to spontaneously revert to the wild-type genetic code.…”