Immunogenicity Of Zoster Vaccine Research Articles

Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies

BackgroundImmunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVIN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). MethodsThis was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZVIN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZVIN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ResultsZVIN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion.Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZVIN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. ConclusionsIn adults with HM receiving anti-CD20 monoclonal antibodies, ZVIN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4.CLINICALTRIALS.GOV identifier: NCT01460719.

Safety, tolerability, and immunogenicity of zoster vaccine in subjects on chronic/maintenance corticosteroids

BackgroundThis randomized, placebo-controlled study assessed the safety, tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals receiving chronic/maintenance systemic corticosteroid therapy (daily dose equivalent of 5–20mg prednisone) for ≥2 weeks prior to vaccination and ≥6 weeks postvaccination. MethodsSubjects were followed for adverse experiences (AEs), exposure to varicella or herpes zoster (HZ), or development of varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination (primary safety follow-up period) and for serious AEs (SAEs) through Day 182 postvaccination (secondary follow-up period). Varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and at Week 6 postvaccination. ResultsThe proportions of subjects reporting systemic AEs and SAEs were similar in both groups. A higher percentage of subjects reported injection-site AEs in the ZV group (21.5%) than in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16 postvaccination) was reported in the ZV group and deemed vaccine-related by the study investigator; however, PCR testing confirmed the presence of wild-type (not vaccine strain) VZV.Geometric mean titer (GMT) at 6 weeks postvaccination was higher for ZV recipients than placebo recipients, with estimated geometric mean fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully. ConclusionsIn adults ≥60 years old on chronic/maintenance corticosteroids, ZV was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks postvaccination were higher in the ZV group than in the placebo group.

Evaluation Methods for the Immunogenicity of Varicella and Zoster Vaccines

Varicella vaccine has been included in the national immunization program for children since 2005 and zoster vaccine has been released since 2012 in Korea. Even though both varicella and zoster are caused by varicella-zoster virus (VZV), pathogeneses are different. In varicella, neutralizing antibody is very important to protect disease because VZV spreads via blood or lymph. In contrast, cell-mediated immunity is more important in zoster because of the neuronal spread of VZV. Therefore, the measurement methods of the immunogenicity against varicella and zoster vaccines are different. Fluorescent antibody to membrane antigen (FAMA) assay is the gold standard method to detect the protective antibody against VZV. It is still used as a reference test for the other methods. However, the fastidious nature required to perform the FAMA assay limits its use as a routine assay for the evaluation of vaccine immunogenicity. Nowadays, glycoprotein ELISA (gpEIA) is used as an alternative method for FAMA assay. However, there is no agreement over the protective level of gpEIA antibody titer with WHO standard international unit. The immunogenicity of zoster vaccine has been evaluated by responder cell frequency assay and IFN-γ ELISpot assay. Nevertheless, skin test is considered to be a more accurate biomarker for cell-mediated immunity against zoster. For the evaluation of varicella vaccine, it is necessary to standardize the FAMA assay and to set the cut-off value for the gpEIA antibody titer through long-term follow-up study. For zoster vaccine, the evaluation of cell-mediated immunity in Korean adults is urgently needed.