LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with Shingrix™ in VZV-primed mice.

Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine Shingrix™ is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with Shingrix™ in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix™ as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to Shingrix™ in a VZV-primed mouse model that was adopted for preclinical studies of Shingrix™. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of Shingrix™ boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.

Varicella-Zoster Virus (VZV) Meningitis in an Immunocompetent Adult after BNT162b2 mRNA COVID-19 Vaccination: A Case Report.

We present, to our knowledge, the second case report of a 46-year old female who developed varicella-zoster virus (VZV) meningitis after BNT162b2 mRNA COVID-19 vaccination. The patient is immunocompetent and has no known predisposing risk factors for developing VZV meningitis. The patient received acyclovir therapy and subsequently had a complete recovery. We describe possible mechanisms of VZV meningitis after mRNA COVID-19 vaccination.

A Case Report of Herpes Zoster Ophthalmicus and Meningitis After COVID-19 Vaccination.

There are several reports that herpes zoster characterized by reactivation of varicella zoster virus (VZV) following coronavirus disease 2019 (COVID-19) vaccines can occur. Herein, we report VZV meningitis, herpes zoster ophthalmicus (HZO), and late neurotrophic keratitis after receiving a second dose of messenger RNA (mRNA) COVID-19 vaccine. A 74-year-old man developed a vesicular skin rash on the forehead, scalp, nose, and left upper eyelid with a severe headache. Five days earlier, he received a second dose of the BNT162b2 mRNA vaccine on his left arm. Ocular examination revealed conjunctival hyperemia and pseudodendrite in the peripheral cornea. VZV was detected in the cerebrospinal fluid using polymerase chain reaction. The patient was diagnosed with HZO and meningitis. The patient was treated with intravenous acyclovir and topical acyclovir ointment and levofloxacin 1.5% eye drops. One month later, he developed a central epithelial defect with a rolled margin, typical of a neurotrophic ulcer. Treatment with a therapeutic contact lens and a combination of topical recombinant human epithelial growth factor and ofloxacin ointment was initiated. At six months after vaccination, the slit-lamp examination findings were stable with a mild corneal superficial stromal haze.

Recurrence of Varicella-Zoster Virus Keratitis After SARS-CoV-2 Vaccination.

PURPOSE: The purpose of this study was to report a case of acute exacerbation in varicella-zoster virus (VZV) keratitis after SARS-CoV-2 vaccination. METHODS: An 87-year-old man, with a history of herpes zoster ophthalmicus 10 years ago, was referred for sudden visual impairment in his left eye that started 2 days after his second dose of SARS-CoV-2 mRNA vaccine BNT162b2. RESULTS: At presentation, his visual acuity was hand motion. Slitlamp examination revealed diffuse corneal stromal edema and nasal stromal infiltration. After treatment for 2 weeks with oral valacyclovir and topical corticosteroids, the problematic lesion was recovered and his visual acuity was restored to 20/30. CONCLUSIONS: We believe that this is the first report of possible association between recurrence of VZV keratitis and SARS-CoV-2 vaccination. We believe that T-cell activation by the host response after vaccination may affect the recurrence of VZV keratitis. Physicians should be aware of the potential of recurrence of VZV keratitis associated with the SARS-CoV-2 messenger RNA vaccine.

Acute Retinal Necrosis from Reactivation of Varicella Zoster Virus following BNT162b2 mRNA COVID-19 Vaccination.

PURPOSE: To report a case of acute retinal necrosis (ARN) due to varicella zoster virus (VZV) after COVID-19 vaccine administration. DESIGN/METHODS: Observational case report. RESULT: A 62-year-old immunocompetent African American male presented with left eye redness, decreased vision, and floaters after receiving a COVID-19 vaccine seven days prior. Slit-lamp examination revealed diffuse fine endothelial keratic precipitates. Funduscopic examination was notable for vitreous cells, occlusive retinal vasculitis, large retinal hemorrhages, and three quadrants of peripheral areas of retinal whitening. Quantitative polymerase chain reaction testing was positive for varicella zoster virus in the vitreous humor. Treatment with intravitreal and intravenous antiviral therapy resulted in symptomatic improvement. CONCLUSION: COVID-19 mRNA vaccination may cause an immunomodulatory response that leads to reactivation of dormant VZV. Early recognition and treatment can improve visual outcomes.

A case of varicella zoster virus meningitis following BNT162b2 mRNA COVID-19 vaccination in an immunocompetent patient.

We report a case of varicella zoster virus (VZV) meningitis following BNT162b2 mRNA COVID-19 vaccination in an immunocompetent patient. A final diagnosis was made based on identification of VZV via positive polymerase chain reaction of cerebrospinal fluid along with characteristic symptoms such as fever, headache, and stiff neck. This phenomenon has been reported elsewhere; this is the 13th such case reported worldwide and the 7th case in immunocompetent patients, indicating the need for careful monitoring after COVID-19 vaccines.

Frequency of putative enteric zoster diagnosed using saliva samples in patients with abdominal pain: a prospective study.

BACKGROUND: Varicella-zoster virus (VZV) infects and establishes latency in neurons in the ganglia of the cranial nerve, dorsal root and enteric ganglia. VZV reactivation in enteric neurons (enteric zoster) can cause non-specific abdominal pain and/or serious gastrointestinal dysfunction without cutaneous manifestations. Detection of VZV DNA in saliva may be useful for identifying enteric zoster. We evaluated the frequency of putative enteric zoster based on the presence of salivary VZV DNA in patients with acute abdominal pain. METHODS: Adult patients who visited the emergency room due to moderate to severe acute abdominal pain were prospectively enrolled at a tertiary hospital between May 2019 and November 2019. Abdominopelvic computed tomography (APCT) was performed in all patients. We also evaluated the presence of salivary VZV DNA in patients with confirmed coronavirus disease-19 (COVID-19) who were under stressful conditions. Saliva samples were collected from all studied patients. Enteric zoster was suspected based on the presence of salivary VZV DNA, detected using real-time polymerase chain reaction (PCR). RESULTS: Fifty patients with moderate to severe abdominal pain were enrolled. Five of 50 patients exhibited positive VZV-DNA PCR results. APCT revealed that among these five patients, two had pancreatic head cancer, two had small bowel obstruction after intra-abdominal surgery, and one had no remarkable findings. However, all 14 patients with COVID-19 showed negative salivary VZV-DNA PCR results. CONCLUSIONS: Approximately 10% of patients with moderate to severe acute abdominal pain showed positivity for salivary VZV DNA. Further studies are warranted on whether antiviral therapy based on salivary VZV-DNA PCR results may relieve abdominal pain in the studied patient population. TRIAL REGISTRATION: clinicaltrial.gov, number NCT03862092.

The influence of immune individuals in disease spread evaluated by cellular automaton and genetic algorithm.

BACKGROUND AND OBJECTIVE: One of the main goals of epidemiological studies is to build models capable of forecasting the prevalence of a contagious disease, in order to propose public health policies for combating its propagation. Here, the aim is to evaluate the influence of immune individuals in the processes of contagion and recovery from varicella. This influence is usually neglected. METHODS: An epidemic model based on probabilistic cellular automaton is introduced. By using a genetic algorithm, the values of three parameters of this model are determined from data of prevalence of varicella in Belgium and Italy, in a pre-vaccination period. RESULTS: This methodology can predict the varicella prevalence (with average relative error of 2%-4%) in these two European countries. Belgium data can be explained by ignoring the role of immune individuals in the infection propagation; however, Italy data can be explained by considering contagion exclusively mediated by immune individuals. CONCLUSIONS: The role of immune individuals should be accurately delineated in investigations on the dynamics of disease propagation. In addition, the proposed methodology can be adapted for evaluating, for instance, the role of asymptomatic carriers in the novel coronavirus spread.