A phase 1 clinical trial has evaluated the safety and immunogenicity of a new varicella vaccine candidate, v7D, which has potential advantages over the current vOka varicella vaccines. v7D has a severely impaired ability to infect human skin and neuronal cells, reducing the risk of varicella-like rashes and vaccine-associated herpes zoster (HZ).
The study included 216 healthy participants aged 1-45 years, randomized to receive either v7D, vOka, or placebo. The vaccine exhibited a good safety profile and was well-tolerated by participants at all three doses tested. Adverse events were mild and resolved quickly. Paired routine blood, liver, or kidney function indexes showed no clinical significance in any v7D vaccine groups.
Additionally, no severe adverse events were judged to be associated with vaccination. Furthermore, negative PCR results for varicella-zoster virus (VZV) DNA in collected saliva samples suggest no or very low viral shedding and, thus, low in vivo replication capacity and virulence of v7D in humans.
Unexpectedly, sero-conversion occurred in four out of five baseline seronegative placebo recipients aged 1-12 years. The study results indicate that the v7D vaccine has potential advantages in clinical safety compared to the vOka vaccine, including lower frequencies of vaccine-associated varicella-like rashes and HZ cases. However, more extensive studies are needed to confirm these results due to the small sample size in this phase 1 clinical trial.
According to a study published in The Lancet Regional Health, the varicella-zoster virus (VZV), which causes the sickness, frequently infects children. VZV can induce herpes zoster (shingles) after reactivation by targeting the sensory nerve ganglia, which has been latent since the first infection (HZ).
HZ significantly reduces the quality of life of people who develop postherpetic neuralgia (PHN) or chronic severe pain. Varicella is expected to kill 4,200 people each year, with another 2.4 million hospitalized due to the condition. Although the frequency of HZ is low in children, it is believed that half of all persons over the age of 85 have had it.
The bulk of commercially available varicella vaccinations is derived from the live-attenuated Oka strain (vOka), which was generated in cell cultures by multiple passages of the original wild-type Oka strain (pOka). Since the United States introduced the varicella vaccine in 1995, more than 43 other nations have followed suit.
Once vaccinations were available to the public, surveillance data revealed their efficacy against various strains of varicella and their generally acceptable safety profile. Yet, the vOka vaccine contains a combination of genetically different VZV variants that may replicate as well as wild-type in nerve tissues and induce rashes similar to varicella.
There are valid safety concerns since vOka can go latent and then reawaken to produce HZ and neurological disorders in some vaccination recipients. The existing vOka vaccine helps to avoid and reduce the illness burden caused by VZV. Still, a varicella vaccine without or with reduced skin- and neuro-pathogenic potential would enhance vaccination uptake and aid in preventing and managing the virus’s spread.
The ORF7 gene is required for VZV infection of human skin and brain cells but not replication in other cell cultures. v7D is considerably attenuated in these tissues due to its inability to replicate or spread from human skin or neural cells in vitro or in SCID-hu mice in vivo, and so meets the crucial safety requirements for the next-generation live varicella vaccine virus, as proven by a preclinical study. v7D immunization has demonstrated immunogenicity equivalent to vOka in mice, rats, guinea pigs, and rabbits.
