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The Journal of Clinical Investigation Dec 2023Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the...
Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients. Compared with ZVL, RZV expanded more gE-specific CD4+ clonotypes, with greater breadth and higher frequency of public clonotypes. RZV recruited a higher proportion of clonotypes from naive than from memory cells, while ZVL recruited equally from memory and naive compartments. Compared with memory-derived, naive-derived clonotypes were more likely to last 5 or more years after immunization. Moreover, the frequency of tetramer+ persistent clones correlated with the frequency of tetramer+ naive CD4+ prevaccination T cells. We conclude that the ability of RZV to recruit naive CD4+ T cells into the response may contribute to the durability of its effect. The abundance, breadth, and frequency of public clonotypes may further add to its protective effect.
Topics: Humans; Aged; Herpes Zoster Vaccine; CD4-Positive T-Lymphocytes; Herpes Zoster; Herpesvirus 3, Human; Vaccination; Vaccines, Synthetic
PubMed: 37788096
DOI: 10.1172/JCI172634 -
Journal of Clinical Virology : the... Aug 2023The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common...
BACKGROUND
The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge.
OBJECTIVE
The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites.
RESULTS
The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel.
CONCLUSION
The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses.
Topics: Humans; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Herpesvirus 6, Human; Virus Diseases; Viruses; Monkeypox virus
PubMed: 37364498
DOI: 10.1016/j.jcv.2023.105525 -
Vaccine Apr 2024Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a... (Review)
Review
Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development. We also discuss the challenges associated with vaccine production in CHO cells, with a focus on ensuring viral clearance for eVLP products.
Topics: Cricetinae; Animals; Humans; CHO Cells; Cricetulus; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Antibodies, Viral; Respiratory Syncytial Virus, Human; Vaccines, Virus-Like Particle; Herpesvirus 3, Human; Vaccines, Subunit; Respiratory Syncytial Virus Vaccines
PubMed: 38503664
DOI: 10.1016/j.vaccine.2024.03.034 -
Journal of Experimental & Clinical... Oct 2023Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1),...
BACKGROUND
Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo.
METHODS
PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment.
RESULTS
Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve ("cold") to inflamed ("hot"), thereby increasing immune cell infiltration and restoring CD8 T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity.
CONCLUSIONS
PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8 T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.
Topics: Humans; Animals; Swine; Mice; Herpesvirus 1, Suid; Vaccines, Attenuated; Mice, Nude; Immune Checkpoint Inhibitors; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; ErbB Receptors; Tumor Microenvironment
PubMed: 37891570
DOI: 10.1186/s13046-023-02848-1 -
American Journal of Obstetrics and... Aug 2023
Topics: Female; Humans; Herpes Zoster; Herpesvirus 3, Human; Vulva
PubMed: 36828295
DOI: 10.1016/j.ajog.2023.02.013 -
Skin Therapy Letter Jul 2023The lifetime risk for herpes zoster (HZ) of approximately 1 in 3 is increased with advancing age, a family history of HZ, diseases with altered immune function,...
The lifetime risk for herpes zoster (HZ) of approximately 1 in 3 is increased with advancing age, a family history of HZ, diseases with altered immune function, immunosuppression, physical trauma and psychological stress. In dermatology, monotherapy with current biologics does not increase risk, however systemic steroids, Janus kinase inhibitors and combination biologic/conventional disease-modifying antirheumatics do. The recombinant zoster vaccine (RZV, Shingrix®), an adjuvanted non-live subunit vaccine against the glycoprotein E subunit of varicella zoster virus, is approved for prevention of HZ in adults ≥50 years of age, and adults ≥18 years of age who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression due to disease or treatment. It is administered as two 0.5 ml intramuscular injections 2-6 months apart. In immunocompromised individuals, the spacing between injections may be reduced to 1-2 months. Where possible, the first dose should be administered at least 14 days before onset of immunosuppressive treatment. Studies in immunocompetent individuals have shown high efficacy including prevention of HZ, postherpetic neuralgia and other complications, with persistence of effect 10 years after vaccination. The acceptable safety profile and efficacy in five different immunocompromised populations support its use in at-risk adult dermatologic patients.
Topics: Adult; Humans; Dermatology; Herpes Zoster; Herpes Zoster Vaccine; Neuralgia, Postherpetic; Herpesvirus 3, Human
PubMed: 37440693
DOI: No ID Found -
Human Vaccines & Immunotherapeutics Dec 2023Herpes zoster (HZ) results from waning immunity following childhood infection with varicella zoster virus (VZV) but is preventable by vaccination with recombinant HZ...
Herpes zoster (HZ) results from waning immunity following childhood infection with varicella zoster virus (VZV) but is preventable by vaccination with recombinant HZ vaccine or live HZ vaccine (two doses or one dose, respectively). Vaccine efficacy declines with age, live HZ vaccine is contraindicated in immunosuppressed individuals, and severe local reactogenicity of recombinant HZ vaccine is seen in up to 20% of older adults, indicating a potential need for new vaccines. Nonreplicating chimpanzee adenovirus (ChAd) vectors combine potent immunogenicity with well-established reactogenicity and safety profiles. We evaluated the cellular and humoral immunogenicity of ChAdOx1 encoding VZV envelope glycoprotein E (ChAdOx1-VZVgE) in mice using IFN-γ ELISpot, flow cytometry with intracellular cytokine staining, and ELISA. In outbred CD-1 mice, one dose of ChAdOx1-VZVgE (1 × 10 infectious units) elicited higher gE-specific T cell responses than two doses of recombinant HZ vaccine (1 µg) or one dose of live HZ vaccine (1.3 × 10 plaque-forming units). Antibody responses were higher with two doses of recombinant HZ vaccine than with two doses of ChAdOx1-VZVgE or one dose of live HZ vaccine. ChAdOx1-VZVgE boosted T cell and antibody responses following live HZ vaccine priming. The frequencies of polyfunctional CD4+ and CD8+ T cells expressing more than one cytokine (IFN-γ, TNF-α and IL-2) were higher with ChAdOx1-VZVgE than with the conventional vaccines. Results were similar in young and aged BALB/c mice. These findings support the clinical development of ChAdOx1-VZVgE for prevention of HZ in adults aged 50 years or over, including those who have already received conventional vaccines.
Topics: Animals; Mice; Herpesvirus 3, Human; Adenovirus Vaccines; Adenoviridae; Antibodies, Viral; Herpes Zoster; Herpes Zoster Vaccine; Vaccination; Cytokines; Immunogenicity, Vaccine
PubMed: 36785938
DOI: 10.1080/21645515.2023.2175558 -
Human Vaccines & Immunotherapeutics Dec 2023The growing burden of herpes zoster (HZ) in Hong Kong, due to an aging population with increasing life expectancy, may be reduced by vaccination. This study aimed to...
The growing burden of herpes zoster (HZ) in Hong Kong, due to an aging population with increasing life expectancy, may be reduced by vaccination. This study aimed to estimate public health impact of HZ vaccination in Hong Kong. The ZOster ecoNomic Analysis (ZONA) model was adapted with Hong Kong-specific key model inputs/assumptions, where available. Base case analysis involved adults ≥50 years of age (YOA), exploring three vaccination strategies (no vaccination/recombinant zoster vaccine [RZV]/zoster vaccine live [ZVL]) under private market (5% coverage) and mass vaccination (40% coverage) settings. Scenario and sensitivity analyses were performed. In the base case population (3.13 million), without vaccination, 891,024 HZ (28.4%), 156,097 post-herpetic neuralgia (PHN) (5.0%), and 38,755 (1.2%) HZ ophthalmicus (HZO) were projected over their remaining lifetime. Mass RZV vaccination reduced HZ, PHN, and HZO cases by 204,875 (-23.0%), 31,949 (-20.5%), and 8,471 (-21.9%), respectively, which was 4-5 times that reduced with ZVL. RZV was more efficient than ZVL, with lower number needed to vaccinate to prevent one HZ/PHN/HZO case (RZV: 7/40/148; ZVL: 27/163/709). Among all age cohorts, the greatest reduction in cases was projected for RZV (versus no vaccination/ZVL) in the youngest cohort, 50-59 YOA. Results were robust under scenario and sensitivity analyses. HZ burden in Hong Kong is substantial. Mass RZV vaccination is expected to considerably reduce public health burden of HZ among individuals ≥50 YOA, compared with no vaccination/ZVL. Results may support value assessment and decision-making regarding vaccination strategies for HZ prevention in Hong Kong.
Topics: Humans; Aged; Herpes Zoster Vaccine; Public Health; Hong Kong; Cost-Benefit Analysis; Herpes Zoster; Neuralgia, Postherpetic; Vaccination; Herpesvirus 3, Human; Vaccines, Synthetic
PubMed: 36854447
DOI: 10.1080/21645515.2023.2176065 -
Vaccine Jul 2023To examine the seroprevalence of measles and varicella zoster virus (VZV) among healthcare workers (HCW) and evaluate the concordance between self-reported history of...
OBJECTIVE
To examine the seroprevalence of measles and varicella zoster virus (VZV) among healthcare workers (HCW) and evaluate the concordance between self-reported history of previous disease or vaccination and seropositivity.
DESIGN
A seroprevalence study and survey.
SETTING
A university-affiliated tertiary care hospital.
PARTICIPANTS
All HCWs working in high-risk services in 2017 underwent serologic tests and survey; all new HCWs employed in the subsequent years, serologic tests only.
METHODS
A serologic study was conducted using chemiluminescence immunoassay (2017) or enzyme immunoassays (2018 and later). HCWs who underwent serological testing in 2017 completed a self-administered questionnaire on their history of infection and vaccination.
RESULTS
A total of 10,278 and 9607 HCWs underwent serologic tests for measles and VZV IgG, respectively, from 2017 to 2022. The overall seropositivity rates for measles and VZV were 78.1 % and 92.8 %, respectively. Measles seropositivity declined gradually from >90 % in the HCWs born in the 1960s to <80 % in those born in the 1990s. There was a significant difference in measles seropositivity between the birth cohorts (BCs) 1967-1984 and 1985-1999 (P < 0.001; odds ratio, 1.16; 95 % confidence interval, 1.14-1.18). The seropositivity for VZV was stable, at >90 % in all BCs. The self-reported vaccination history was not independently associated with seropositivity, and the negative predictive value of the survey was very low (9.6 % and 13.1 %, respectively).
CONCLUSIONS
Measles seropositivity showed a substantial decline among HCWs born in 1985 or later, while varicella seropositivity remained high. The self-reported vaccination history was not sufficiently reliable for screening HCWs.
Topics: Humans; Herpesvirus 3, Human; Seroepidemiologic Studies; Chickenpox; Health Personnel; Measles; Republic of Korea; Antibodies, Viral
PubMed: 37349224
DOI: 10.1016/j.vaccine.2023.06.018 -
Cleveland Clinic Journal of Medicine Oct 2023
Topics: Humans; Chickenpox; Herpesvirus 3, Human; Herpes Zoster; Vaccines
PubMed: 37783498
DOI: 10.3949/ccjm.90a.23008