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1.
PLoS One ; 19(8): e0309154, 2024.
Article in English | MEDLINE | ID: mdl-39159217

ABSTRACT

INTRODUCTION: The incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection. METHODS: We used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection. RESULTS: The weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8). DISCUSSION: Varicella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks.


Subject(s)
Chickenpox , Humans , Chickenpox/epidemiology , Chickenpox/immunology , Chickenpox/prevention & control , Adolescent , Child , Child, Preschool , Female , Male , Canada/epidemiology , Adult , Young Adult , Middle Aged , Infant , Chickenpox Vaccine/immunology , Vaccination , Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , Herpesvirus 3, Human/immunology
2.
Hum Vaccin Immunother ; 20(1): 2367283, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39051458

ABSTRACT

As of 2024, Thailand has not incorporated the varicella-zoster virus (VZV) vaccine into the Expanded Program on Immunization (EPI). This study aimed to evaluate VZV seroprevalence across all age groups in Chonburi Province, Thailand, during the post-COVID-19 era, and to support the development of a vaccination plan against VZV. A total of 950 participants were enrolled from October 2022 to January 2023. VZV antibody levels were measured using ELISA kits (EUROIMMUN, Lübeck, Germany), with seropositivity set at ≥110 IU/L. The overall VZV seropositivity rate was 64.8%, similar to rates in 1994 and 2014. However, seropositivity rates for the 5-9, 10-14, and 15-19 age groups were significantly higher in the 1994 study, and for the 10-14 and 15-19 age groups in the 2014 study, indicating a declining trend among young Thai individuals. The seropositivity rate increased with age, with a seroprevalence exceeding 80% in individuals aged 30 years and older. Our study found a significant association between the history of varicella and seropositivity. Thus, a positive history may indicate immunity. In conclusion, a significant portion of Thai adolescents are still vulnerable to varicella, highlighting the crucial role of vaccination in averting serious illness.


Subject(s)
Antibodies, Viral , COVID-19 , Herpesvirus 3, Human , Humans , Seroepidemiologic Studies , Thailand/epidemiology , Adolescent , Child , Young Adult , Adult , Antibodies, Viral/blood , Male , Female , Child, Preschool , Herpesvirus 3, Human/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , Middle Aged , Aged , Chickenpox/epidemiology , Chickenpox/immunology , Chickenpox/prevention & control , Infant , Vaccination/statistics & numerical data
3.
Hum Vaccin Immunother ; 20(1): 2364485, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39053454

ABSTRACT

The objective of the study is to analyze the implementation effect of the Live Attenuated Varicella Vaccine (VarV) Vaccination Program for eligible children in Bao'an District, Shenzhen, and evaluate the vaccine effectiveness. Children's vaccination data was obtained from the Shenzhen Immunization Planning Information Management System, while varicella case data came from the China Disease Prevention and Control Information System. The Joinpoint regression method examined vaccination rate trends, and a retrospective cohort study assessed vaccine effectiveness. After program implementation, VarV vaccination rates significantly increased, surpassing provincial and national averages. Overall incidence declined 54.6% across age groups, with the largest reductions among 7- and 6-year-olds. One year post-vaccination, single-dose vaccine effectiveness was 91.1% (95% CI: 79.2% to 96.2%). However, two doses remained 91.4% effective(95% CI: 89.1% to 93.2%) after 7 years. Overall, Shenzhen's VarV program achieved positive results. For children under six, routine immunization with two doses of VarV should be strengthened. Furthermore, we recommend that physicians conduct thorough inquiries to ascertain patients' vaccination history and previous varicella infections. This will enable doctors to provide tailored vaccination recommendations based on comprehensive, practical evaluations.


Subject(s)
Chickenpox Vaccine , Chickenpox , Immunization Programs , Vaccination , Vaccines, Attenuated , Humans , Chickenpox Vaccine/administration & dosage , Chickenpox Vaccine/immunology , China/epidemiology , Child , Vaccines, Attenuated/immunology , Vaccines, Attenuated/administration & dosage , Female , Male , Chickenpox/prevention & control , Chickenpox/epidemiology , Chickenpox/immunology , Retrospective Studies , Vaccination/statistics & numerical data , Child, Preschool , Vaccine Efficacy , Adolescent , Incidence
4.
J Neurovirol ; 30(3): 327-335, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39085748

ABSTRACT

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that causes neurological manifestations either as a complication of primary infection or reactivation. VZV induced neurological diseases have a good prognosis when confirmed early and treated with anti-viral therapy. Myelitis, encephalitis, ventriculitis or meningitis can occur without a telltale rash in immunocompetent and immunocompromised individuals making the diagnosis difficult. We analyzed CSF and serum samples from 30 unvaccinated study participants (17 male and 13 female) to determine the presence of VZV DNA by PCR in CSF and to estimate serum and CSF anti-VZV IgG and albumin levels in participants with neurological manifestations with/without rash. Anti-VZV IgG was detected in CSF (n = 22, [73%]) and serum (n = 29, [97%]) of pediatric and adult participants. Anti-VZV IgG were detected in CSF of participants with varied clinical presentation altered sensorium (n = 8, [36%]), meningitis (n = 4, [18%]), acute febrile illness (n = 3, [14%], encephalopathy/meningoencephalitis (n = 2, [9%]), irritability (n = 2, [9%]) and each patient from cerebrovascular stroke, demyelinating disorder and febrile seizure (n = 1, [4.5%]). VZV DNA was detected from one participant and CSF serum albumin levels were elevated in 53% of study participants. VZV DNA is present up to 1-2 weeks post onset of disease, after which anti-VZV antibody may be the only indicator of disease and therefore both VZV DNA and anti-VZV IgG need to be tested for in CSF. As VZV DNA and VZV IgG antibody are both good indicators of VZV reactivation, routine testing would result in reduced morbidity and mortality by early detection of disease and antiviral treatment.


Subject(s)
Antibodies, Viral , Herpesvirus 3, Human , Immunoglobulin G , Humans , Male , Female , Herpesvirus 3, Human/immunology , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Adult , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Adolescent , Middle Aged , Child , Child, Preschool , DNA, Viral/blood , DNA, Viral/cerebrospinal fluid , Young Adult , Aged , Chickenpox/virology , Chickenpox/immunology , Chickenpox/diagnosis , Chickenpox/blood , Infant
5.
Rev Med Virol ; 34(4): e2554, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862398

ABSTRACT

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.


Subject(s)
Herpesvirus 3, Human , Humans , Herpesvirus 3, Human/immunology , Herpesvirus 3, Human/physiology , Herpesvirus 3, Human/pathogenicity , Herpes Zoster/virology , Herpes Zoster/immunology , Varicella Zoster Virus Infection/immunology , Varicella Zoster Virus Infection/virology , Nervous System Diseases/virology , Nervous System Diseases/immunology , Nervous System Diseases/etiology , Animals , Chickenpox/virology , Chickenpox/immunology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/virology
6.
Viruses ; 16(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38932134

ABSTRACT

OBJECTIVE: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. METHODS: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). RESULTS: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. CONCLUSION: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.


Subject(s)
Antibodies, Viral , Chickenpox Vaccine , Vaccines, Attenuated , Humans , Male , Female , Vietnam , Child , Chickenpox Vaccine/immunology , Chickenpox Vaccine/adverse effects , Chickenpox Vaccine/administration & dosage , Antibodies, Viral/blood , Antibodies, Viral/immunology , Infant , Vaccines, Attenuated/immunology , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/administration & dosage , Child, Preschool , Vaccination , Chickenpox/prevention & control , Chickenpox/immunology , Immunogenicity, Vaccine , Herpesvirus 3, Human/immunology , Southeast Asian People
7.
Vaccine ; 42(22): 125996, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-38824086

ABSTRACT

BACKGROUND: Immunization against vaccine-preventable diseases prior to pregnancy is an important measure of primary prevention both for the mother and the unborn child. We analyzed immunity rates against measles, mumps, rubella, varicella, and pertussis in pregnant employees in Germany prior to significant changes in legal conditions in 2020, to provide a basis of comparison for future research. METHODS: We analyzed occupational-medical routine data in three collectives of pregnant women with an occupational risk of infection in the years 2018 and 2019: 1: hospital staff with regular access to an in-house company physician (n = 148); 2: employees in childcare with regular access to external occupational-health services (n = 139); 3: teachers with no regular access to occupational healthcare (n = 285). Immune status was assessed by a physician based on vaccination certificates, laboratory results, and medical documentation on prior infections. We compared immunity rates against measles, rubella, varicella, and pertussis as well as full immunity against all targeted vaccine-preventable diseases. RESULTS: Altogether, n = 572 pregnant women were included in our study. Of these women, 96.5 % were immune to rubella, 95.8 % to varicella, 88.3 % to measles, 82.7 % to mumps, and 67.8 % to pertussis. Only 56.2 % of the women had full immunity against all targeted vaccine-preventable diseases. Collective 1 showed the highest immunity rates against measles and pertussis as well as the highest rate of full immunity against all targeted vaccine-preventable diseases. The immunity rates against rubella and varicella did not differ significantly between the collectives. With the exception of rubella, the lowest immunity rates during pregnancy were found in Collective 3. CONCLUSION: We found pregnancy-relevant immunity gaps in all our study groups with significant differences between the collectives. Considering the potentially devastating consequences of infections during pregnancy, all medical professionals and health-policy makers should be involved in an increased effort to improve vaccination rates prior to pregnancy.


Subject(s)
Chickenpox , Measles , Rubella , Vaccination , Vaccine-Preventable Diseases , Humans , Female , Germany/epidemiology , Pregnancy , Measles/prevention & control , Measles/immunology , Adult , Rubella/prevention & control , Rubella/immunology , Chickenpox/prevention & control , Chickenpox/immunology , Chickenpox/epidemiology , Vaccine-Preventable Diseases/prevention & control , Vaccine-Preventable Diseases/immunology , Vaccine-Preventable Diseases/epidemiology , Mumps/prevention & control , Mumps/immunology , Pregnant Women , Whooping Cough/prevention & control , Whooping Cough/immunology , Young Adult
8.
Front Public Health ; 12: 1375151, 2024.
Article in English | MEDLINE | ID: mdl-38784578

ABSTRACT

Introduction: Homeless individuals suffer a high burden of vaccine-preventable infectious diseases. Moreover, they are particularly susceptible to adverse infection outcomes with limited access to the health care system. Data on the seroprevalence of measles, mumps, rubella, and varicella within this cohort are missing. Methods: The seroprevalence of measles, mumps, rubella, and varicella was determined within the homeless population in Germany. Predictors of lacking immune protection were determined using multivariable logistic regression analysis. Results: Homeless individuals in Germany (n = 611) showed a seroprevalence of 88.5% (95% CI: 85.8-91.0) for measles, 83.8% (95% CI: 80.6-86.6) for mumps, 86.1% (95% CI: 83.1-88.7) for rubella, and 95.7% (95% CI 93.8-97.2) for varicella. Measles seroprevalences declined from individuals born in 1965 to individuals born in 1993, with seroprevalences not compatible with a 95% threshold in individuals born after 1980. For mumps, seroprevalences declined from individuals born in 1950 to individuals born in 1984. Here, seroprevalences were not compatible with a 92% threshold for individuals born after 1975. Seronegativity for measles, mumps and rubella was associated with age but not with gender or country of origin. Discussion: Herd immunity for measles and mumps is not achieved in this homeless cohort, while there was sufficient immune protection for rubella and varicella. Declining immune protection rates in younger individuals warrant immunization campaigns also targeting marginalized groups such as homeless individuals. Given that herd immunity thresholds are not reached for individuals born after 1980 for measles, and after 1975 for mumps, vaccination campaigns should prioritize individuals within these age groups.


Subject(s)
Chickenpox , Ill-Housed Persons , Measles , Mumps , Rubella , Humans , Male , Female , Mumps/immunology , Mumps/epidemiology , Cross-Sectional Studies , Germany/epidemiology , Ill-Housed Persons/statistics & numerical data , Adult , Measles/epidemiology , Measles/immunology , Rubella/immunology , Rubella/epidemiology , Seroepidemiologic Studies , Middle Aged , Chickenpox/epidemiology , Chickenpox/immunology , Young Adult , Vaccination/statistics & numerical data , Adolescent , Aged
9.
Lancet Infect Dis ; 24(8): 922-934, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38614117

ABSTRACT

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
Antibodies, Viral , Chickenpox Vaccine , Chickenpox , Vaccines, Attenuated , Humans , Chickenpox Vaccine/immunology , Chickenpox Vaccine/administration & dosage , Chickenpox Vaccine/adverse effects , Double-Blind Method , Vaccines, Attenuated/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/adverse effects , Male , Female , Child, Preschool , Child , Antibodies, Viral/blood , Chickenpox/prevention & control , Chickenpox/immunology , China , Herpesvirus 3, Human/immunology , Immunogenicity, Vaccine , Vaccination/methods
10.
Eur J Clin Microbiol Infect Dis ; 43(6): 1139-1148, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38613705

ABSTRACT

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.


Subject(s)
Antibodies, Viral , Chickenpox , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Luminescent Measurements , Measles virus , Measles , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Measles/diagnosis , Measles/immunology , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Luminescent Measurements/methods , Enzyme-Linked Immunosorbent Assay/methods , Child , Male , Female , Adult , Adolescent , Chickenpox/diagnosis , Chickenpox/immunology , Measles virus/immunology , Child, Preschool , Young Adult , Middle Aged , Herpesvirus 3, Human/immunology , Sensitivity and Specificity , Infant , Aged , Immunoassay/methods , Reagent Kits, Diagnostic/standards
11.
J Virol ; 96(22): e0131022, 2022 11 23.
Article in English | MEDLINE | ID: mdl-36314824

ABSTRACT

During childhood, the composition and function of the T cell compartment undergoes significant changes. In healthy individuals, primary infection with herpesviruses is followed by latency, and occasional subclinical reactivation ensures transmission and contributes to an emerging pool of memory T cells. In immunocompromised individuals, herpesviruses can be life threatening. However, knowledge about the spectrum of virus-specific cytokine responses is limited. Here, we investigated peripheral blood mononuclear cells (PBMCs) from children with differential carrier statuses for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and varicella zoster virus (VZV) (n = 32, age 1 to 17 years). We examined memory T cell subsets as well as IFN-γ-, IL-10-, IL-17A-, and IL-22-producing T cells after polyclonal activation or stimulation with viral peptides using flow cytometry and a 4-parameter FluoroSpot assay. Age and herpesvirus carriage influenced the size of the memory T cell subsets. A positive association between age and the number of IFN-γ-, IL-17A- and IL-22-producing T cells was found following polyclonal activation. For CMV, age was positively associated with IL-17A spot-forming cells (SFC), while for VZV, age was negatively associated with IL-22 and positively associated with IFN-γ SFC. Upon activation with CMV, VZV, and EBV peptides, IFN-γ SFCs dominated. Notably, VZV responses were characterized by a higher IL-10 SFC population compared to both CMV and EBV. Our findings suggest that cytokine responses vary across herpesvirus-type-specific memory T cells and may more adequately reflect their composition. An observed deviation between polyclonal and herpesvirus-specific T cell cytokine responses in children needs to be considered when interpreting the associations between herpesvirus carrier status and bulk T cell reactivity. In summary, these findings may have implications for the treatment of immunocompromised patients. IMPORTANCE Infection with herpesviruses accounts for 35 to 40 billion human cases worldwide. Despite this, little is known about how herpesviruses shape the immune system in the asymptomatic carrier. Particularly in children, primary infection is connected to no or mild symptoms ahead of latency for life. Most research on cellular responses against herpesviruses focuses on inflammatory cytokines associated with antiproliferative and antitumor mechanisms and not the spectrum of cytokine responses in healthy humans. This study investigated four divergent cytokine-producing T cell responses to herpesviruses, reflecting different immunological functions. Three common childhood herpesviruses were selected: Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus. Curiously, not all viruses induced the same pattern of cytokines. Varicella-zoster responses were characterized by IL-10, which is considered regulatory. Besides broadening understanding of responses to herpesviruses, our results raise the possibility that reactivation of varicella-zoster may be counterproductive in cancer treatment through the action of IL-10-producing T-cells.


Subject(s)
Chickenpox , Cytomegalovirus Infections , Epstein-Barr Virus Infections , Interleukin-10 , Memory T Cells , Adolescent , Child , Child, Preschool , Humans , Infant , Chickenpox/immunology , Cytomegalovirus , Cytomegalovirus Infections/immunology , Epstein-Barr Virus Infections/immunology , Herpes Zoster , Herpesvirus 3, Human , Herpesvirus 4, Human , Interleukin-10/immunology , Interleukin-17 , Leukocytes, Mononuclear , Memory T Cells/immunology , Simplexvirus
12.
Nat Commun ; 13(1): 824, 2022 02 11.
Article in English | MEDLINE | ID: mdl-35149692

ABSTRACT

Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns. Here, we rationally design a live-attenuated varicella vaccine candidate, v7D. This virus replicates like wild-type virus in MRC-5 fibroblasts and human PBMCs, the carrier for VZV dissemination, but is severely impaired for infection of human skin and neuronal cells. Meanwhile, v7D shows immunogenicity comparable to vOka both in vitro and in multiple small animal species. Finally, v7D is proven well-tolerated and immunogenic in nonhuman primates. Our preclinical data suggest that v7D is a promising candidate as a safer live varicella vaccine with reduced risk of vaccine-related complications, and could inform the design of other herpes virus vaccines.


Subject(s)
Chickenpox Vaccine/immunology , Chickenpox/immunology , Skin/immunology , Vaccines, Attenuated/immunology , Animals , Cell Line , Chickenpox/prevention & control , Female , Fibroblasts , Guinea Pigs , Herpes Zoster/virology , Herpesvirus 3, Human , Humans , Immunogenicity, Vaccine , Lung , Male , Mice , Neurons/pathology , Rabbits , Rats , Skin/pathology , Vaccination , Viral Vaccines
13.
J Korean Med Sci ; 36(36): e222, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34519184

ABSTRACT

BACKGROUND: Despite high coverage (~98%) of universal varicella vaccination (UVV) in the Republic of Korea since 2005, reduction in the incidence rate of varicella is not obvious. The study aimed to evaluate the vaccine effectiveness (VE) of one-dose UVV by timeline and severity of the disease. METHODS: All children born in Korea in 2011 were included for this retrospective cohort study that analyzed insurance claims data from 2011-2018 and the varicella vaccination records in the immunization registry. Adjusted hazard ratios by Cox proportional hazard models were used to estimate the VE through propensity score matching by the month of birth, sex, healthcare utilization rate, and region. RESULTS: Of the total 421,070 newborns in the 2011 birth cohort, 13,360 were matched for age, sex, healthcare utilization rate, and region by the propensity score matching method. A total of 55,940 (13.29%) children were diagnosed with varicella, with the incidence rate 24.2 per 1000 person-year; 13.4% of vaccinated children and 10.4% of unvaccinated children. The VE of one-dose UVV against any varicella was 86.1% (95% confidence interval [CI], 81.4-89.5) during the first year after vaccination and 49.9% (95% CI, 43.3-55.7) during the 6-year follow-up period since vaccination, resulting in a 7.2% annual decrease of VE. The overall VE for severe varicella was 66.3%. The VE of two-dose compared to one-dose was 73.4% (95% CI, 72.2-74.6). CONCLUSION: We found lower long-term VE in one-dose vaccination and waning of effectiveness over time. Longer follow ups of the vaccinated children as well as appropriately designed studies are needed to establish the optimal strategy in preventing varicella in Korea.


Subject(s)
Chickenpox Vaccine/administration & dosage , Chickenpox/prevention & control , Vaccine Efficacy/statistics & numerical data , Birth Cohort , Chickenpox/epidemiology , Chickenpox/immunology , Chickenpox/pathology , Chickenpox Vaccine/immunology , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Propensity Score , Republic of Korea/epidemiology , Retrospective Studies , Severity of Illness Index , Vaccination
14.
Nutrients ; 13(3)2021 Mar 02.
Article in English | MEDLINE | ID: mdl-33801237

ABSTRACT

Treatment with prebiotics, a type of dietary fiber, was recently shown to increase antibody concentrations following influenza vaccination in a meta-analysis of clinical trials. In observational epidemiologic studies it is not possible to estimate intake of prebiotics, but quantifying intake of dietary fiber is routine. Our objective was to investigate the potential effect of dietary fiber on immunogenicity. We examined serum antibody concentrations (Measles, Mumps, Rubella, and Varicella) in relation to dietary fiber in more than 12,000 subjects in the U.S. National Health and Nutrition Examination Survey (NHANES) for the period 1999-2004. Data from one (1999-2002) or two (2003-2004) dietary recalls were used to calculate fiber intake. For Mumps the adjusted percentage difference in antibody concentration per interquartile range intake in energy-adjusted dietary fiber was 6.34% (95% confidence interval, 3.10, 9.68). Fiber from grain-based foods was more positively associated than fiber from other fiber-containing food groups. The association was slightly larger among subgroups with higher fiber intake, greater interquartile range in fiber intake, and less measurement error. Furthermore, based on the reliability of the diet recalls in 2003-2004, we calculated that the percentage difference per interquartile increment was substantially attenuated by measurement error. Dietary fiber may have a favorable influence on the immunogenicity of some vaccines or natural infections.


Subject(s)
Antibodies, Viral/blood , Chickenpox/immunology , Dietary Fiber , Measles/immunology , Mumps/immunology , Nutrition Surveys , Rubella/immunology , Adolescent , Adult , Chickenpox/prevention & control , Child , Cross-Sectional Studies , Epidemiologic Studies , Female , Humans , Immunogenicity, Vaccine , Male , Measles/prevention & control , Middle Aged , Mumps/prevention & control , Rubella/prevention & control , Vaccination , Young Adult
15.
J Prim Care Community Health ; 12: 21501327211005902, 2021.
Article in English | MEDLINE | ID: mdl-33813919

ABSTRACT

OBJECTIVES: The purpose of this cohort study was to evaluate measles, mumps, rubella (MMR), and varicella immunity among a population of adult employees receiving primary care in an employer-sponsored health center. METHODS: Participants were eligible for MMR and varicella immunity screening if they were an employee receiving primary care in an employer-sponsored health center between January 1, 2019 and November 1, 2020 who could not provide proof of immunization and 1) had it recommended by their provider, 2) specifically requested immunity testing (often because they had heard of measles outbreaks in their country of origin), or 3) were seen for an immigration physical for their Green Card application. RESULTS: Overall, 3494 patients were screened for their MMR immunity. Of these, 3057 were also screened for varicella immunity. Among these patients, 13.9% lacked measles immunity, 0.83% lacked immunity to all 3 components of MMR, and 13.2% lacked varicella immunity. Among the 262 patients who presented specifically for immunity screening, the rates of lacking immunity were higher for all conditions: 22.7% lacked measles immunity and 9.2% lacked varicella immunity. CONCLUSION: Given declines in immunizations during the COVID-19 pandemic, there is reason to be concerned that measles and varicella-associated morbidity and mortality may rise. Employers, especially those with large foreign-born populations or who require international travel may want to educate their populations about common contagious illnesses and offer immunity validation or vaccinations at no or low cost.


Subject(s)
COVID-19 , Chickenpox , Measles , Mumps , Pandemics , Rubella , Vaccination Coverage , Adult , Antibodies, Viral , California , Chickenpox/immunology , Chickenpox/prevention & control , Cohort Studies , Disease Outbreaks , Female , Humans , Male , Mass Screening , Measles/immunology , Measles/prevention & control , Mumps/immunology , Mumps/prevention & control , Occupational Health Services , Primary Health Care , Rubella/immunology , Rubella/prevention & control , SARS-CoV-2 , Vaccination
16.
Evid. actual. práct. ambul ; 24(4): e002147, 2021.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1361868

ABSTRACT

A partir de 2022, a la dosis de vacuna contra la varicela contemplada a los 15 meses de edad en el Calendario Nacional de Vacunación de Argentina, se suma una segunda dosis al ingreso escolar. En este artículo se repasan los aspectos clave para la implementación de esta práctica de inmunización universal, gratuita y obligatoria. (AU)


Starting in 2022, a second dose of the varicella vaccine will be added to the 15-month-old dose included in Argentina's National Vaccination Schedule at school entry. This article reviews the key aspects for the implementation of this universal, free and mandatory immunization practice. (AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Chickenpox/prevention & control , Immunization Schedule , Chickenpox Vaccine/administration & dosage , Argentina , Chickenpox/immunology
17.
Rev. Asoc. Esp. Espec. Med. Trab ; 29(2): 23-28, jun. 2020. tab, graf
Article in Spanish | IBECS | ID: ibc-193750

ABSTRACT

INTRODUCCIÓN Y OBJETIVOS: Garantizar la seguridad y salud de los estudiantes de enfermería que realizan prácticas en el hospital ofreciéndoles vacunación hasta alcanzar el nivel inmunológico de protección necesario. METODOLOGÍA: Revisión y recogida de datos de las historias clínico-laborales de 182 estudiantes de la Escuela de Enfermería de Sacyl en Zamora (2016-2019). RESULTADOS: Todos acreditan estar vacunados según calendario oficial. Tras primera serología, el 31,6% no presenta inmunidad frente a la triple vírica, el 2,15% frente a la varicela y el 86,9% frente a la vacuna de la hepatitis B. El 7,1% resultó no respondedor frente a la vacuna de la hepatitis B tras segunda pauta vacunal completa. CONCLUSIONES: La realización de la serología en el cribado prevacunación permite revacunar a aquellos que no presentan inmunización así como detectar aquellos casos no respondedores que tendrán un manejo adecuado si ocurre un accidente con exposición a una fuente de alto riesgo


INTRODUCTION AND OBJETIVES: Ensure the safety and health of nursing students who practice in the hospital by providing them with vaccinations up to the necessary immune protection level. METHODOLOGY: Review and data collection from the clinical- workplace histories of 182 students of the Sacyl School of Nursing in Zamora (2016-2019). RESULTS: All of them certify to be vaccinated according to official calendar. After the first serology, 31.6% did not have immunity against the triple virus, 2.15% against chickenpox and 86.9% against the hepatitis B vaccine. 7.1% were not responding to the hepatitis B vaccine after the second complete vaccination. CONCLUSION: The realization of serology in the screening allows to revaccinate those who don't present immunization, as well as detect those non-responders who will have adequate management if an accident with exposure to a high-risk source occurs


Subject(s)
Humans , Students, Nursing/statistics & numerical data , Vaccination/statistics & numerical data , Hepatitis B Vaccines/blood , Chickenpox/blood , Chickenpox/immunology , Hepatitis B Vaccines/immunology , Occupational Health/statistics & numerical data , Spain
18.
Ital J Pediatr ; 46(1): 75, 2020 May 29.
Article in English | MEDLINE | ID: mdl-32471468

ABSTRACT

INTRODUCTION: Varicella may complicate with cerebellitis in previously healthy children, requiring hospitalization. Aim of our study was to define whether children who experienced varicella cerebellitis have a normal immune system. METHODS: Patients over 3 years of age admitted at Bambino Gesù Children from January 2006 till June 2016 for cerebellitis in varicella were asked to participate to the follow-up study. The immune status was evaluated clinically and by laboratory investigations. RESULTS: Twenty-five patients were included in the study. At follow up, at least one immunological alteration was detected in 80% of patients. To avoid bias due to possible effects of the recent disease, we separately analyzed patients who had the follow-up control at least 1 year (Group 1) or between 1 month and 1 year (Group 2) after the hospitalization for acute varicella cerebellitis. The results were similar in both groups with immunological alterations detected in 84,6 and 75% of the patients, respectively. CONCLUSIONS: Our preliminary results indicate that sub-clinical immunological defects may correlate to cerebellitis in varicella.


Subject(s)
Cerebellar Diseases/immunology , Cerebellar Diseases/virology , Chickenpox/immunology , Encephalitis, Varicella Zoster/immunology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Risk Factors
19.
Tohoku J Exp Med ; 250(3): 181-190, 2020 03.
Article in English | MEDLINE | ID: mdl-32213753

ABSTRACT

Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69+T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8+T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4+T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4+T-cells. In conclusion, the decreased numbers of VZV-specific CD8+T-cells during the acute phase and VZV-specific CD4+T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.


Subject(s)
Chickenpox/immunology , Chickenpox/virology , Herpesvirus 3, Human/immunology , T-Lymphocytes/immunology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Chickenpox/drug therapy , Child , Child, Preschool , Convalescence , Humans , Immunocompetence , Immunosuppressive Agents/therapeutic use , Infant , Interferon-gamma/metabolism , Lectins, C-Type/metabolism , Lymphocyte Activation/immunology , Lymphocyte Count , Species Specificity , Tissue Donors
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