VZV Vaccination Research Articles

Repurposing varicella zoster virus and human papillomavirus vaccines for local immunotherapy against solid tumors

Abstract Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor microenvironment (TME) and anti-tumor immunity. We assessed in situ vaccination with licensed subunit vaccines to leverage preexisting anti-vaccine immunity in a tumor model expressing HPV16 viral oncogenes E6 and E7. We chose Shingrix, a VZV vaccine containing the glycoprotein E (gE), and Gardasil-9, an HPV vaccine containing the L1 virus-like particles (VLP) to preferentially induce CD4 and CD8 T cell responses, respectively. Intratumoral (IT) injection of Shingrix in prevaccinated mice often led to complete regression and elicited CD8 T cell responses against E7. IT injection of an MHC-II-restricted gE peptide with polyI:C also led to durable remission, suggesting a role for gE-specific CD4 T cells. In contrast, IT injection of Gardasil-9 did not delay tumor growth, but IT injection of an MHC-I-restricted L1 peptide with Shingrix led to complete remissions hence overcoming preexisting antibodies against native HPV VLP. TME analysis showed that IT injection of Shingrix with Gardasil-derived peptide induced IFN-g, TNF-a and CXCL9 and reshaped the myeloid cell infiltrate. Finally, IT injection of Shingrix and the E7 viral neoantigen peptide led to the eradication of all primary injected and abscopal tumors. Our results indicate that Shingrix is a versatile component for in-situ vaccination which can be combined with peptides derived from licensed vaccines or tumor antigens.

Abstract LB353: Repurposing varicella zoster virus and human papillomavirus vaccines for local immunotherapy against solid tumors

Abstract Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor microenvironment (TME) and anti-tumor immunity. We assessed in situ vaccination with licensed subunit vaccines to leverage preexisting anti-vaccine immunity in the TC-1 tumor model expressing HPV16 viral oncogenes E6 and E7. We chose Shingrix, a VZV vaccine containing the glycoprotein E (gE), and Gardasil-9, an HPV vaccine containing L1 virus-like particles (VLP), to preferentially induce CD4 and CD8 T cell responses, respectively. Intratumoral (IT) injection of Shingrix in Shingrix prevaccinated mice led to complete regression in 20% to 50% of treated mice and elicited CD8 T cell responses against the viral oncoprotein E7. IT injection of an MHC-II-restricted gE peptide with polyI:C also led to durable remission, suggesting that gE-specific CD4 T cells played a significant role in tumor control. In contrast, IT injection of Gardasil-9 in Gardasi-9 prevaccinated animals did not delay tumor growth. However, IT injection of an MHC-I-restricted L1 peptide with Shingrix consistently led to complete remissions perhaps by overcoming preexisting antibodies against native HPV VLP which appeared to inhibit the cross-presentation of VLP derived antigens. TME analysis showed that IT injection of Shingrix with Gardasil-derived peptide induced IFN-gamma, TNF-alpha and CXCL9. This treatment also dramatically reshaped the immune cell infiltrate causing the recruitment of T cells and neutrophils and the decrease of tumor-associated macrophage and eosinophils. We are investigating now how these changes may contribute to tumor clearance and epitope spreading against tumor-derived antigens. Finally, IT injection of Shingrix and a E7 viral neoantigen peptide led to the eradication of all primary injected and abscopal tumors. Our results indicate that the ability of Shingrix to induce exceptionally strong Th1 responses makes it a versatile component for in-situ vaccination which can be combined with peptides derived from licensed vaccines or tumor antigens. Because this approach relies on relatively low cost existing vaccines and inexpensively manufactured minimal CD8 restricted peptides, it has the potential for a broadly applicable cancer immunotherapy strategy for use in resource-constrained settings. The approach is currently being evaluated in a phase I clinical trial in companion dogs with spontaneously arising cancers. Citation Format: Nicolas Cuburu, Shiv K. Sethi, Claire E. Bradley, Lukas Bialkowski, Cynthia D. Thompson, Douglas R. Lowy, John T. Schiller. Repurposing varicella zoster virus and human papillomavirus vaccines for local immunotherapy against solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB353.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients

Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Antiviral vaccines for local immunotherapy against solid tumors

Abstract Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor immune microenvironment and anti-tumor immunity. Here, we interrogate whether preexisting anti-vaccine immunity induced by licensed subunit vaccines could be leveraged for local cancer immunotherapy in the syngeneic murine tumor models. We selected Shingrix, a VZV vaccine containing the glycoprotein E (gE) antigen and adjuvant AS01B, and Gardasil-9, a HPV vaccine containing the L1 virus-like particles and alum because of the CD4 and CD8 T cell responses they respectively induce. Intratumoral injection of Shingrix alone or with immune checkpoint blockade (CTLA-4), in prevaccinated mice delayed tumor growth and often led to complete regression. These responses were associated with the induction of CD8+ T cell responses against tumor associated antigen, to tumor immune activation and alteration of the myeloid compartment. The injection of selected MHC-II-restricted gE minimal peptide epitopes combined with polyI:C also led to durable remission suggesting a contribution of gE-specific CD4 T cells. In contrast, Gardasil-9 i.t. injection did not delay tumor growth or cause tumor rejection which suggests inefficient class I cross-presentation of native VLP in the tumor cells. However, the injection of MHC-I-restricted L1 minimal peptide epitopes led to complete and durable remissions suggesting efficient tumor control by L1-specific CD8 T cells. Our results suggest that anti-viral licensed vaccines can be leverage as a new class of immunotherapeutics for local cancer therapy and intrinsic immunogenicity properties of vaccines should be considered as these effects appeared to be vaccine specific. NIH Intramural program.

2158. Monitoring of Varicella specific T-cell mediated immunity in pediatric allogenic hematopoietic stem cell transplant recipients

Abstract Background Varicella-zoster virus (VZV) infection is known to occur in 13-55% of patients within the first year after hematopoietic stem cell transplant (HSCT). The dynamics of recovery of VZV-specific T cell- mediated immunity (CMI) and its role for prevention and control of VZV reactivation are rarely reported in pediatric allogenic HSCT recipients. Methods From April 2019 to February 2020, subjects aged younger than 19 years who underwent allogenic HSCT with at least 1 year of follow up at Asan Medical Center Children`s Hospital were prospectively enrolled. All of them underwent VZV-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before HSCT and then at 1, 3 months following HSCT. Extension study, which measures VZV-specific CMI before and after VZV vaccination at 24 months post-HSCT, is currently underway. Results A total of 32 HSCT recipients with a median age of 11years were enrolled. 37.5% underwent haploidentical HSCT and VZV R+ were in 78.1%. Antiviral prophylaxis was applied to all HSCT recipients, of which 65.6% were applied up to 365 days after HSCT. During this study period, only 1 patient (3.1%) experienced herpes zoster at 23 months following HSCT, whose VZV-specific ELISPOT assay showed 0, 1, and 0 spot-forming cells (SFC)/2.0x105 cells before HSCT, 1 and 3 months following HSCT, respectively. The presence of VZV-specific CMI ≥ 1 SFC/ 2.0 × 105 cells was observed in 62.5 % before HSCT, 65.6 % at 1 month, 59.4 % at 3 months, and 70% at 24 months after HSCT, respectively. However, only 18.8 % ,12.5 % and 21.9 % recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cells at 1, 3 and 24 months following HSCT. Meanwhile, all the 4 recipients who got the 1st VZV vaccination at 24 months following HSCT showed recovery of VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell. Recovery of VZV-specific CMI after HSCT was not associated with VZV serostatus, chickenpox history, type of HSCT, conditioning regimens, and GVHD. Conclusion Only a few pediatric allogenic HSCT recipients recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell up to 2 years following HSCT. In addition, the association between VZV-specific CMI and VZV reactivation could not be analyzed because no one experienced VZV reactivation within 1 year after HSCT. More long-term large-scale multicenter study is mandatory to supplement these parts. Disclosures All Authors: No reported disclosures.

Recurrent facial palsy: Characteristics of ipsilateral and alternative palsies of 104 cases

ObjectiveRecurrent facial palsy is relatively rare and its clinical details of recurrent facial palsy are not well known. We analyzed recurrent facial palsy cases and clarified its characteristics, especially the difference between ipsilateral and alternative palsies. The analysis aimed to obtain information about recurrent facial palsy that would be useful for delivering explanations to patients and help improve recurrent facial palsy treatments based on the etiology. MethodsWe picked up data from the chart and analyzed the clinical characteristics of patients with recurrent facial palsy from 1243 facial palsy patients (Bell's palsy, VZV-related palsy (Ramsay Hunt syndrome and zoster sine herpete [ZSH])) between 2006 and 2020. ResultsRecurrent facial palsy was observed in 104 of 1243 patients (8.4%). There were 35 cases (34%) of ipsilateral palsy and 69 cases (66%) of alternative palsy. The mean age at the onset of the first palsy was 38.9 years old in the ipsilateral group and 48.4 years old in the alternative group, and a significant difference was observed between them. The number of recurrences ranged from 1 to 4. Among the ipsilateral group, 6 patients experienced more than second recurrence. In two cases, the condition failed to resolve after the second recurrence. A serological examination confirmed that 4 cases had recurrent VZV-related palsy (both the first and second palsies were VZV-related) and all of them initially had ZSH: no cases had Hunt syndrome as the first palsy. ConclusionsThe VZV-specific immunity obtained with ZSH might be insufficient to suppress VZV reactivation, and VZV vaccination should be recommended for ZSH patients to prevent further recurrence of VZV-related facial palsy. More than 2 ipsilateral recurrent episodes may be a risk factor for incomplete recovery.

S12 Development of Shingles on Tofacitinib Despite Completion of Recombinant VZV Vaccination Series

S12 Development of Shingles on Tofacitinib Despite Completion of Recombinant VZV Vaccination Series

Serologic evaluation of vaccine preventable infections and vaccination rates in kidney transplant candidates.

Assessing vaccine serologic status presents opportunities to provide live vaccinations to kidney transplant candidates (KTC). This is especially important given the increased risk of infection while taking lifelong immunosuppression following transplant and the inability to routinely provide live vaccines to patients on immunosuppressive medications. In March 2019, the American Society of Transplantation Infectious Disease Community of Practice (AST-IDCOP) released updated guidelines for vaccination of KTC, which emphasize pretransplant viral serology screening and live vaccine administration prior to transplant. The primary endpoint of this study was to determine adherence to AST-IDCOP guidelines for live measles, mumps, and rubella (MMR) and VZV vaccination prior to transplant in KTC non-immune by serology. This retrospective, descriptive study examined serologic status and rates of live vaccination in 672 patients listed for kidney transplant at our center between July 2014 and July 2019. Secondary endpoints included subgroup analysis of adherence to full AST-IDCOP vaccination recommendations and validation of CDC presumed immunity definitions for measles and VZV. Seventeen patients (2.7%) were nonimmune by serology for VZV, while 182 (27.1%) were nonimmune by serology to MMR. In a subgroup analysis of the seronegative KTC, none received VZV vaccination, and 6% received MMR vaccination prior to transplant or last follow-up. Overall, a large portion of KTC had immunity gaps that were not resolved before transplantation. These findings are limited due to the retrospective, single-center nature of this study and should be confirmed with larger, prospective assessments of serologic status and vaccine administration.

Early experience with varicella vaccination in pediatric heart transplant recipients.

International consensus guidelines to vaccinate children after solid organ transplant with the live-attenuated varicella (VZV) vaccine exclude pediatric heart transplant recipients due to insufficient evidence for safety, seroconversion rate, or adverse event profile. Caution is also recommended in the setting of mycophenolate mofetil (MMF) immunosuppression. However, VZV infection in these patients can be serious or even fatal. We report our novel early experience with VZV vaccination in a cohort of 31 children following heart transplantation, 42% of who were on MMF. The early seroconversion rate was 16/17 (94%) with no major adverse events. Though a rash of some description was reported in 29%, spots were few and self-resolving in 1-3 days. Select pediatric heart transplant patients can be safely vaccinated with VZV vaccine with a high early seroconversion rate and a mild adverse event profile.

Low post‐transplant measles and varicella titers among pediatric liver transplant recipients: A 10‐year single‐center study

Vaccine preventable illnesses are important sources of morbidity, mortality, and increased healthcare costs in pediatric LT recipients. Our aim was to measure the seroprevalence of antibodies to measles and VZV in this population. We conducted a retrospective chart review of 44 patients who received LT before age 18 at UCLA Mattel Children's Hospital from January 2008 to December 2017. Median age at transplantation was 2.5 years (IQR 1.2-7.7). Post-transplant measles antibodies were present in 17 of 37 patients (46%); risk factors for seronegativity included younger age at transplant (p= .02) and greater time from transplant to testing (p= .04). Post-transplant VZV antibodies were present in 17 of 39 patients (44%); risk factors for seronegativity included greater time from transplant to testing (p= .04). 6 of 16 patients (38%) who tested positive for pre-transplant VZV antibodies tested negative after transplantation. Fourteen of 20 patients (70%) with at least 1 documented dose of the MMR vaccine tested positive for post-transplant measles antibodies. Ten of 20 of patients (50%) with at least 1 documented dose of the VZV vaccine tested positive for post-transplant VZV antibodies. We also describe 10 patients who received post-transplant measles and VZV vaccines without documented complications. Our study suggests that pediatric LT patients are at greater risk of contracting measles and VZV despite vaccination status, and that prevalence of measles and VZV antibodies decreases as time from transplantation increases. This should weigh into the institutional risk-benefit assessment when deciding whether or not to administer LAVs to these patients.

Studies of Infection and Experimental Reactivation by Recombinant VZV with Mutations in Virally-Encoded Small Non-Coding RNA.

Locked-nucleotide analog antagonists (LNAA) to four varicella zoster virus small non-coding RNA (VZVsncRNA 10–13) derived from the mRNA of the open reading frame (ORF) 61 gene individually reduce VZV replication in epithelial cells and fibroblasts. To study the potential roles VZVsncRNA 10–13 have in neuronal infection we generated two recombinant VZV; one in which 8 nucleotides were changed in VZVsncRNA10 without altering the encoded residues of ORF61 (VZVsnc10MUT) and a second containing a 12-nucleotide deletion of the sequence common to VZVsncRNA12 and 13, located in the ORF61 mRNA leader sequence (VZVsnc12-13DEL). Both were developed from a VZV BAC with a green fluorescent protein (GFP) reporter fused to the N terminal of the capsid protein encoded by ORF23. The growth of both mutant VZV in epithelial cells and fibroblasts was similar to that of the parental recombinant virus. Both mutants established productive infections and experimental latency in neurons derived from human embryonic stem cells (hESC). However, neurons that were latently infected with both VZV mutant viruses showed impaired ability to reactivate when given stimuli that successfully reactivated the parental virus. These results suggest that these VZVsncRNA may have a role in VZV latency maintenance and/or reactivation. The extension of these studies and confirmation of such roles could potentially inform the development of a non-reactivating, live VZV vaccine.

Implementation of EACS vaccination recommendations among people living with HIV

ObjectivesWith modern combination antiretroviral Treatment (cART) a normal life expectancy among people living with HIV (PLWH) has become reality if started early enough prior to the onset of more pronounced immunodeficiency. Therefore, prevention measures against other infectious diseases among this vulnerable group have gained increased attention. Indeed, the EACS guidelines recommend vaccinations against HAV, HBV, HPV, Influenza, Neisseria meningitidis, Streptococcus pneumoniae and VZV in HIV-infected adults.MethodsAll PLWH under cART attending our ID outpatient clinic between April to June 2018, were assessed during consultation for vaccination status regarding pneumococcus, Hepatitis A and B, influenza, varicella, meningococcus and HPV using a pre-defined questionnaire, vaccination certificates and medical records. In addition, the cohort database was screened for Hepatitis A and B serology and HIV surrogate markers.ResultsA total of 305 PLWH (82.3% male, 17.7% female) was included, median age was 48 years (IQR 47–51). Median CD4 + T cell count was 543 (IQR 304–770), and for 297 (97.4%) PLWH CD4 + T cell count was ≥ 200/ul. The viral load was undetectable (< 40 copies/ml) in 289 (94.8%) cases. Highest vaccination rates were observed for HAV (87.4%), Streptococcus pneumoniae (77.4%) and Influenza (76.5%). 64.3% PLWH got vaccinated against HBV, whereas VZV vaccination only played a minor role, in the context of the high rate of cleared infections (99.0%). Lowest vaccination rates were detected for HPV (0%) and Neisseria meningitidis (3.0%).ConclusionsOur data suggest that vaccination rates among PLWH are higher compared to the general German population. Implementation of EACS guidelines into daily routine though is not fully executed and the need for improving vaccination rates has to be emphasized. Centrally organized vaccination registers as well as electronic medical records could be helpful tools to detect a lack of vaccination coverage and send digital vaccination reminders particularly among risk groups.

An Overview of Herpes zoster: Aetiology, Pathogenesis and Treatment

Varicella zoster virus is one of the eight herpes viruses that are pathogenic only for humans. It is alpha-herpes zoster of the genus varicellovirus, which causes varicella (chickenpox) and zoster (shingles). Herpes zoster is described as a multivesicular eruptive rash that follows a single or multiple adjacent dermatomal distribution. VZV infection begins with replication in epithelial cells of upper respiratory mucosa, which is followed by widely distributed vesicular rash. Cell-mediated immunity plays a role in this reactivation. Patients with conditions that decrease cell-mediated immunity are 20 to 100 times more prone to develop herpes zoster. It is often accompanied by acute pain and itchiness. Complications may be dermatological (e.g. secondary bacterial infection), neurological (e.g. long-term pain, segmental paresis, stroke), ophthalmological (e.g. keratitis, iridocyclitis, secondary glaucoma) or visceral (e.g. pneumonia, hepatitis). Most common Complications of the infection are post herpetic neuralgia and ophthalmic zoster. Treatment includes antiviral medications such as acyclovir, famciclovir, and valacyclovir given within 72 hours of symptom has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia, both these diseases are vaccine preventable. Before the invention of the recombinant VZV vaccine, live VZV vaccine was the recommended immunization, approved for adults 50 years and older.

Convalescent plasma in patients hospitalised with COVID-19

Convalescent plasma in patients hospitalised with COVID-19

Effect of varicella zoster vaccine vs candida antigen injection in treatment of warts.

Treatment of warts is considered as a big challenge for patients as well as doctors. Immunotherapy represents a promising and successful method of warts treatment. A great attention has been paid for various types of immunotherapeutic agents. One of the immunotherapeutic approaches is intralesional immunotherapy that showed a successful result in treatment of warts. Complete resolution of warts was achieved in many of studied patients, while some of them showed partial response and only few patients showed no response. Our study was based on the previous observations and reports of regression of several types of warts after administration of candida antigen and other new immunotherapeutic antigens. Candida antigen group showed complete clearance in 16 patients (69.6%), partial response in seven patients (30.4%). In VZV vaccine group, complete clearance was observed in 15 patients (65.2%), partial response in eight patients (34.8%). These results showed that the therapeutic response in two groups had a close statistical result and more chances must be given to VZV vaccine specially after its promising and successful results. In conclusion, we presented a novel approach for the treatment of recalcitrant wart using intralesional immunotherapy with Candida antigen and VZV vaccine. VZV vaccine seems to be promising, safe and effective remedy for any type warts mainly plantar warts.

EPID-06. QUANTIFYING THE POTENTIAL PUBLIC HEALTH IMPACT OF VARICELLA ZOSTER VIRUS (VZV) VACCINATION ON GLIOMA INCIDENCE

Abstract BACKGROUND Varicella zoster virus (VZV) is a neurotropic a-herpesvirus that causes chickenpox and establishes latency in the dorsal root ganglion. Live attenuated VZV vaccine was approved for use in 1995, with the CDC estimating 95% of teens had been vaccinated in 2014. Prior epidemiological literature suggests an association between VZV infection and glioma risk. METHODS We conducted a systematic review and meta-analysis of prior studies on the association between VZV infection and glioma risk. We also identified genetic instruments for VZV infection from prior GWAS and tested these for association with glioma risk in TCGA and GliomaScan (2244 cases, 4914 controls). RESULTS In six previous studies, individuals with positive chickenpox history or anti-VZV IgG seropositivity had 1.8-fold lower odds of glioma (ORmeta=0.55, 95%Cl=0.39–0.77), with similar effects by grade. GWAS hits for personal history of chickenpox (HLA-A Gly107 and rs9266089) and shingles (HLA-AArg97, HLA-DRB1 PheSerHis13, rs2523591, rs41316748 and rs7047299) were not associated with glioma risk, nor were polygenic scores (P &amp;gt;0.05). DISCUSSION Prior VZV infection is associated with reduced glioma risk and, based on analysis of genetic instruments, this appears to be an acquired protection caused by VZV infection rather than innate immunologic differences. VZV infection in known to elicit a broader antibody response than vaccination, but it is unknown whether VZV vaccination provides comparable protection against glioma. Because 89% of U.S. adults have had chickenpox, the “prevented fraction” of glioma due to chickenpox is ~29% of annual incidence. If VZV vaccination confers an equivalent 1.8-fold reduction in glioma risk, this prevented fraction could increase to 32%. However, if VZV vaccination is less protective, it could decrease to just 2%. This potentially drastic increase in glioma incidence in coming decades merits mechanistic studies comparing the neuro-immunologic consequences of VZV vaccination versus chickenpox infection and warrants early public health attention.

Characterization of binding of Varicella zoster virus vaccine strains to preparations of mouse brain membrane receptors

Purpose: characterization of vFiraVax (the causative agent of chickenpox - VZV) and vZelVax (the causative agent of shingles - HZ) vaccine strains by their ability to bind to preparations of brain membrane receptors of SPF BALB/c mice.Materials and Methods. The study was performed on cold-adapted vFiraVax VZV and vZelVax HZ vaccine strains developed by the authors on the basis of the wild-type parental pFira VZV virus (chickenpox causative agent) and the latent parental lpZel HZ virus (shingles causative agent); vOka vaccine strains isolated from vaccines against VZV infection from two manufactures (United Kingdom and USA); the HEL-3 strain of diploid cells from human embryonic lung tissue, the MC 27 strain of diploid cells from human embryonic musculocutaneous tissue, primary and diploid cells from guinea pig fetal fibroblasts. The VZV infectivity was estimated by the limiting dilution method using MC 27 cell cultures or guinea pig fetal fibroblasts. The virus titer was measured by the hemadsorption test performed with suspensions of red blood cells from guinea pig or human type 0 positive blood. Negative staining and electron microscopy were used to study the virus preparation. The immunogenicity of vFiraVax VZV and vZelVax HZ virus strains was compared with the immunogenicity of vOka VZV virus strains from different manufacturers by using a cross-neutralization test with immune sera.Results. The Russian cold-adapted vFiraVax VZV and vZelVax HZ vaccine strains, the latent parental lpZel HZ virus and the vOka VZV vaccine strain (United Kingdom) did not bind to preparations of brain neuroreceptors of SPF BALB/c mice as distinct from the wild-type parental pFira VZV variant and vOka VZV vaccine strains (USA); the absent neurotropism of Russian vFiraVax VZV and vZelVax HZ vaccine strains is not connected with the decreased immunogenicity in relation to foreign counterparts; the electron microscope study of the vFiraVax VZV virus containing liquid concentrate detected VZV nucleocapsids.Conclusion. The differences in the VZV ability to bind to preparations of brain membrane receptors of SPF BALB/c mice can be explained by the differences in the technology of vaccine manufacturing, including attenuation techniques, obtaining of the vaccine strain, specific characteristics of the latent parental lpZel HZ virus. The absence of the binding with brain neuroreceptors of SPF mice has been proved for the Russian vFiraVax VZV and vZelVax HZ vaccine strains which was is not connected with a decrease in their immunogenicity. The method of assessment of the binding ability of VZV vaccine strains can be used as a preliminary characteristic of neurotropism for newly created vaccine strains and for vaccine products.

Women who received varicella vaccine versus natural infection have different long-term T cell immunity but similar antibody levels

BackgroundVaricella-zoster virus (VZV) infection during pregnancy is associated with serious fetal anomalies. The live-attenuated VZV vaccine was approved in 1995, so many vaccinated women are now of childbearing age. The question of long-term immunity to varicella is critical because breakthrough chickenpox can occur after vaccination. ObjectiveTo compare humoral and T cell immunity between women of childbearing age who were immunized by vaccination or chickenpox disease. Study designNon-pregnant females between 18 and 36 years old with a history of VZV immunization (n = 20) or prior chickenpox disease (n = 20) were recruited. IgG antibody titers and T cell responses were measured by flow cytometry-based methods in serum and peripheral blood, respectively. ResultsThere were no significant differences in median antibody titers between vaccinated and chickenpox groups (p = 0.34). The chickenpox group had significantly higher levels of VZV antigen-specific CD4 T cells (p = 0.004). ConclusionNatural infection induced higher VZV-specific T cell immune responses than vaccination.

Vaccination rate and immunity of children and adolescents with inflammatory bowel disease or autoimmune hepatitis in Germany

Background and aimsImmunosuppressed patients are at risk of severe infections with vaccination preventable diseases. We evaluated vaccination rate and immunity of children and adolescents with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). MethodsImmunization rate of 329 children with IBD (n = 300) and AIH (n = 29) was assessed in seven German centres using vaccination certificates, history of chicken pox and by determining anti-varicella zoster virus (VZV) and anti-measles IgG antibodies. ResultsOf the total cohort 86% received long-term immunosuppression. Four doses of a hexavalent vaccine were documented in 89%, at least one dose of measles, mumps, and rubella (MMR) vaccination was documented in 325 (99%), with 300 (92%) receiving two doses. Anti-measles IgG concentrations were insufficient in 11% of the immunized patients.VZV vaccination was officially recommended in Germany since 2004, and implemented in 88% born from 2005 onwards. In patients born earlier VZV catch up vaccination only reached 25% (n = 67). Of 118 patients with documented VZV vaccination 25 (21%) did not display sufficient anti-VZV IgG. Of 198 patients with a history of chicken pox, six had undetectable anti-VZV IgG. Of 29 patients having neither had chicken pox nor VZV vaccination, 20 were found to have sufficient anti-VZV IgG. ConclusionsIn our cohort vaccination coverage for hexavalent and MMR vaccinations was good, but insufficient for VZV vaccination in patients born before 2005. Neither the vaccination certificate nor the history of chicken pox is reliable to predict VZV immunity indicating a need for serologic investigations and if needed vaccination before initiating immunosuppressive therapy.

2301. Increased Risk of Varicella-Associated Hospitalizations Among Adult Immigrants From Temperate and Tropical Countries After the Introduction of a Childhood Varicella Vaccination Program in Quebec, Canada

BackgroundVaricella zoster virus (VZV) hospitalizations are an uncommon, severe and costly consequence of VZV. Childhood VZV vaccination leads to decreased VZV rates across all age groups through herd immunity but increases the age of VZV acquisition and the potential risk of severe VZV in non-immune adults. A large proportion (~15%) of young adult immigrants from tropical regions are susceptible to VZV due to different transmission dynamics in their countries of origin and lack of vaccination. We aimed to describe the impact of the childhood VZV program introduced in 2006 in Quebec on VZV hospitalizations in immigrants and nonimmigrants.MethodsA population-based cohort of all medically-attended VZV cases in Quebec, Canada (1996–2014) were identified in administrative health databases and linked to immigration data. VZV-attributable hospitalizations included those with primary or secondary ICD-9 or ICD-10 codes for VZV. Overall age-standardized and age-specific rates of hospitalizations were calculated during pre- (1996–98), private (1999–2005) and public vaccination (2006–14) periods and by immigrant status and pregnancy. Relative risk (RRI-NI) and 95% CI for immigrants vs. nonimmigrants were estimated.Results5873 hospitalizations occurred among 230,052 VZV cases. Hospitalization rates decreased dramatically in the pre to public vaccination period (6.6 to 1.3/100,000 population); however, the proportion of hospitalized varicella cases increased from 1.7% to 3.9% (P < 0.01). Immigrants only accounted for 3.6% of hospitalizations (N = 213) however, the proportion of all hospitalizations among immigrants increased in the pre- vs. public-vaccination periods in those aged 10–19 years (2.9% to 13.7%) and 20–39 years (8.8% to 22.7%). The RR was higher in these age groups in the public vaccination period [RRI-NI 1.96 and RRI-NI 1.67] (Table 1). Adults (>20 years) accounted for 52% (CI: 45–59%) and pregnant women 18% (13–25%) of all hospitalizations among immigrants compared with only 14% (13–15%) and 1.6% (1.3–2.0%) in nonimmigrants, respectively.ConclusionYoung adult and pregnant immigrants bore a disproportionate burden of VZV hospitalizations after the introduction of childhood VZV vaccination. Susceptible immigrant adults would benefit from targeted VZV vaccination. Disclosures All authors: No reported disclosures.