scholarly journals Persistence of Immune Response to an Adjuvanted Varicella-Zoster Virus Subunit Candidate Vaccine for up to Year 9 in Older Adults

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S415-S415 ◽  
Author(s):  
Karlis Pauksens ◽  
Stephanie Volpe ◽  
Tino F Schwarz ◽  
Jan Smetana ◽  
Nicole Toursarkissian ◽  
...  
Keyword(s):  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Geometric Mean ◽  
Intracellular Cytokine Staining ◽  
Post Dose ◽  
Serious Adverse Events ◽  
Activation Markers ◽  
Varicella Zoster ◽  
Age Cohorts ◽  
Humoral Immune

Abstract Background In the ZOE-50 and ZOE-70 clinical trials, the candidate herpes-zoster subunit vaccine (HZ/su; 50µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) demonstrated high efficacy against HZ, with limited waning over 4 years and consistent efficacy across age cohorts. In adults ≥60 years of age, the immune responses elicited by 2 HZ/su doses administered 2 months apart persisted for at least 6 years.1 Here we report immunogenicity and safety 9 years post-initial vaccination. Methods This Phase IIIB, open, long-term extension study (NCT02735915) followed 70 participants who received 2 HZ/su doses in the initial trial (NCT00434577). Blood samples to evaluate the persistence of cellular (intracellular cytokine staining) and humoral (ELISA) immune responses were taken at 9 years post-initial vaccination. Limited safety follow-up was performed (1 visit). Results All 70 participants (mean age at dose 1: 72.3 years; 61.4% female) were included in the according-to-protocol analysis. The fold increases over pre-vaccination in the frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued after 4 years post-dose 1 (year 4: 3.4, year 5: 3.0, year 6: 3.4, year 9: 3.4). Anti-gE antibody geometric mean concentrations were also stable from year 4 onwards (Table 1) and remained above the pre-vaccination value of 1213.1mIU/mL. Cellular and humoral responses at year 9 were similar across age strata (60–69, ≥70 years). No vaccine-related serious adverse events nor suspected HZ episodes were reported. Conclusion In adults ≥60 years of age, HZ/su-induced cellular and humoral immune responses remained above pre-vaccination levels for at least 9 years post-initial vaccination, confirming immune persistence predictions2 based on 6-year data. Disclosures S. Volpe, GSK: Employee, Salary; T. F. Schwarz, GSK: Investigator and Scientific Advisor, Consulting fee; J. Smetana, GSK: Investigator, personal fees; 
S. Ravault, GSK: Employee, GSK shares and Salary; M. P. David, GSK: Employee, Salary and stock; A. Bastidas, GSK: Employee, Salary; L. Oostvogels, GSK: Employee and Shareholder, Salary and shares

scholarly journals 2905. Long-term Immunological Persistence of the Adjuvanted Recombinant Zoster Vaccine: Clinical Data and Mathematical Modeling

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S84-S85 ◽  
Author(s):  
Adriana Bastidas ◽  
Grégory Catteau ◽  
Stéphanie Volpe ◽  
Tomas Mrkvan ◽  
Adaora Enemuo ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Immune Responses ◽  
Median Frequency ◽  
Zoster Vaccine ◽  
Activation Markers ◽  
Age Cohorts ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Recombinant Zoster Vaccine ◽  
Extension Trial

Abstract Background The adjuvanted recombinant zoster vaccine (RZV, GSK), administered to adults ≥ 50 years of age (YOA) demonstrated ≥ 90% efficacy against herpes zoster across all age cohorts. Vaccine-specific immune responses elicited by two RZV doses in adults ≥ 60 YOA have been shown to persist above pre-vaccination levels at least up to 9 years after initial vaccination. Here we present persistence of the humoral and cellular immunity and safety up to 10 years after initial vaccination as well as data from mathematical modeling, performed to predict immune persistence up to 15 years. Methods This phase IIIB, open-label extension trial (NCT02735915) included 70 participants who had received two RZV doses in the initial trial (NCT00434577) and builds on a previous extension trial (NCT01295320). Cellular and humoral immune responses up to year 10 after an initial 2-dose vaccination schedule are presented here. Additionally, prediction of immunological persistence at year 15 was assessed by mathematical modeling (Piecewise, Power-law, Fraser), using the individual subject values for available data up to year 10. Results The median frequency of varicella-zoster virus glycoprotein E (gE)-specific CD4+ T-cells expressing ≥ 2 activation markers plateaued at 3.3-fold above pre-vaccination levels starting around year 4 up to year 10 post-initial vaccination. Anti-gE antibody concentrations plateaued starting around year 3 up to year 10 post-initial vaccination.Ten years after initial vaccination, humoral responses remained 5.9-fold higher as compared with pre-initial vaccination levels (Figure 1). No relevant safety events were identified during the study (year 9–10 post-initial vaccination). In line with previous modeling data, the year 10 analysis predicts that both cellular and humoral immune responses will remain above pre-vaccination levels for at least 15 years after initial vaccination (Figures 2 and 3). Conclusion In adults vaccinated when ≥ 60 YOA, humoral and cellular immune responses induced by two RZV doses persist above pre-vaccination levels for at least 10 years post-initial vaccination. Mathematical modeling predicts a maintained vaccine-related immune response for at least 15 years after initial vaccination. Funding. GlaxoSmithKline Biologicals SA. Disclosures All Authors: No reported Disclosures.

scholarly journals High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine

2015 ◽  
Vol 22 (5) ◽  
pp. 570-577 ◽  
Author(s):  
Julia Sarkadi ◽  
Mate Jankovics ◽  
Kinga Fodor ◽  
Zoltan Kis ◽  
Maria Takacs ◽  
...  
Keyword(s):  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Mrna Expression ◽  
Guinea Pigs ◽  
Neutralizing Antibodies ◽  
Granzyme B ◽  
Inactivated Vaccine ◽  
Varicella Zoster ◽  
Humoral Immune ◽  
Ifn Γ

ABSTRACTThe threat of varicella and herpes zoster in immunocompromised individuals necessitates the development of a safe and effective varicella-zoster virus (VZV) vaccine. The immune responses of guinea pigs to the intradermal (i.d.) or subcutaneous (s.c.) administration of a heat-inactivated or live VZV vaccine were investigated. Relative to nonimmunized animals, a single 399-PFU dose of vaccine induced nonsignificant increases in gamma interferon (IFN-γ), granzyme B, and perforin mRNA expression in the splenocytes of all groups, while two i.d. administrations of the inactivated vaccine increased IFN-γ mRNA expression significantly (P< 0.005). A single 1,995-PFU dose significantly increased the expression of IFN-γ mRNA in the groups receiving the vaccine either i.d. (P< 0.005) or s.c. (P< 0.05), that of granzyme B mRNA in the groups immunized i.d. with the inactivated (P< 0.005) or live (P< 0.005) vaccine, and that of perforin mRNA in the animals that received the inactivated vaccine i.d. (P< 0.005). Importantly, increases in the expression of IFN-γ (P= 0.025), granzyme B (P= 0.004), and perforin (P> 0.05) mRNAs were observed in the animals immunized i.d. with 1,995 PFU of inactivated vaccine relative to those immunized s.c. with the same dose. The proportion of animals expressing IFN-γ mRNA mirrored the proportion expressing IFN-γ protein (correlation coefficient of 0.88). VZV glycoprotein-specific and virus-neutralizing antibodies were produced with no significant intergroup differences. A booster i.d. administration of the 399-PFU dose of heat-inactivated vaccine enhanced the antibody responses. These results demonstrate that i.d. administration of an inactivated VZV vaccine can be an efficient mode of immunization against VZV.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Herpes zoster recurrence within 1 month: A case report

2021 ◽  
Vol 19 ◽  
pp. 205873922110212
Author(s):  
Nan Zhao ◽  
Yulan Geng ◽  
Yexian Li ◽  
Lijuan Liu ◽  
Yanjia Li ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Case Report ◽  
Herpes Zoster ◽  
B Cells ◽  
Varicella Zoster Virus ◽  
Lower Limit ◽  
Skin Disease ◽  
Clinical Manifestations ◽  
Varicella Zoster ◽  
Humoral Immune

Herpes zoster (HZ), caused by the varicella-zoster virus, is an infectious skin disease that rarely recurs after initial presentation. The mechanism underlying HZ recurrence is currently under investigation. In this article, we report a case of HZ relapse within 1 month. Analysis of patient’s clinical manifestations, histopathological features, and flow cytometry results indicated that the absolute and percentage values of B cells were below the lower limit. We hypothesized that the patient had abnormal humoral immune function, which may be one reason leading to the HZ relapse within 1 month. The findings of this case will serve as useful reference for HZ recurrence for clinicians. This case was impactful and added to the literature on HZ recurrence.

Long-Term Protective Immunity of Recipients of the OKA Strain of Live Varicella Vaccine

PEDIATRICS ◽  
1985 ◽  
Vol 75 (4) ◽  
pp. 667-671 ◽  
Author(s):  
Yoshizo Asano ◽  
Takao Nagai ◽  
Takao Miyata ◽  
Takehiko Yazaki ◽  
Shigemitsu Ito ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Skin Reaction ◽  
Protective Immunity ◽  
Geometric Mean ◽  
Varicella Vaccine ◽  
Geometric Mean Titer ◽  
Positive Skin ◽  
Varicella Zoster ◽  
Mean Diameter

In spite of close contacts with patients who had varicella, 101 of 106 (95%) healthy and sick children (142 of 147 (97%) exposures of these children) who had received the OKA strain of live varicella vaccine 7 to 10 years earlier were protected against the disease completely. Among them, 37 of 38 (97%) vaccine recipients who received immunologic testing had varicella-zoster virus (VZV) antibodies tested by fluorescent antibody to membrane antigen method with a geometric mean titer of 1:9.3, and 37 of the 38 (97%) showed positive skin reaction to varicella-zoster virus antigen with erythema (mean diameter 13.4 mm). These findings were compared with those for 29 children who had contracted typical varicella 7 to 10 years earlier, whose seropositive rate was 100% with a geometric mean titer of 1:10.5, and 97% of whom (28/29) had positive skin reaction with mean diameter of 12.9 mm. These results indicate that the vaccine-induced protective immunity persists for approximately one decade and is almost equal to the long-term immunity following natural infection.

scholarly journals Varicella‐Zoster Virus–Specific Immune Responses to Herpes Zoster in Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine

2009 ◽  
Vol 200 (7) ◽  
pp. 1068-1077 ◽  
Author(s):  
Adriana Weinberg ◽  
Jane H. Zhang ◽  
Michael N. Oxman ◽  
Gary R. Johnson ◽  
Anthony R. Hayward ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Zoster Vaccine ◽  
Varicella Zoster

scholarly journals Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients

2016 ◽  
Vol 60 (10) ◽  
pp. 6252-6259 ◽  
Author(s):  
John S. Bradley ◽  
Jon Armstrong ◽  
Antonio Arrieta ◽  
Raafat Bishai ◽  
Shampa Das ◽  
...  
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Pediatric Patients ◽  
Geometric Mean ◽  
Open Label ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Age Cohorts ◽  
Concentration Time ◽  
Systemic Antibiotic Therapy

ABSTRACTThis study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0–∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

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